Novel immunogenic compositions for the prevention and treatment of meningococcal disease

专利摘要:
The present invention provides an immunogenic portion of a Neseria ORF2086 protein, a biological equivalent thereof, an antibody that immunospecifically binds to it, which can be isolated from a Neisseria strain or can be recombinantly produced. Neseria ORF2086 protein comprising a nucleic acid sequence encoding each of the above, as well as its use in immunogenic compositions effective against infection by Neisseria meningitidis serogroup B.
公开号:KR20040066793A
申请号:KR10-2004-7005313
申请日:2002-10-11
公开日:2004-07-27
发明作者:게리 더블유. 즐로트닉；레아 디. 플레처；존 팔리；리셀 에이. 베른필드；로버트 제이. 자구르스키；벤자민 제이. 메트칼프
申请人:와이어쓰 홀딩스 코포레이션；
IPC主号:

专利说明:

New immunogenic compositions for the prevention and treatment of meningococcal disease {NOVEL IMMUNOGENIC COMPOSITIONS FOR THE PREVENTION AND TREATMENT OF MENINGOCOCCAL DISEASE}
[2] Meningococcal meningitis is a terrible disease that can kill children and young adults within hours despite the availability of antibiotics (Pizza et al., 2000, Science 287: 1816-1820). Meningitis is characterized as inflammation of the meninges resulting from intense headaches, fever, loss of appetite, intolerance to light and sound, muscle stiffness, especially muscle stiffness in the neck, and in severe cases cramping, vomiting and death. Signs of meningococcal meningitis appear suddenly, leading to meningococcal sepsis with its characteristic hemorrhagic rash. Instantaneous diagnosis and immediate treatment with large amounts of antibiotics are critical when there is any chance of survival (2000. Bantam Medical Dictionary, Third Edition 302).
[3] Meningococcal meningitis is caused by Neisseria meningitidis (meningococcal), a Gram-negative encapsulated bacterium classified into several pathogenic serogroups, including A, B, C, D, W-135, X, Y, Z and 29E. do. yen. The serogroup B strain of meningitidis is a major cause of meningococcal disease throughout the world. For example, the medical literature reports that serogroup B causes about 50% of bacterial meningitis among infants and children residing in the United States and Europe. yen. There is currently no vaccine to prevent meningococcal disease caused by Meningitidis serogroup B.
[4] Development of immunogenic compositions for the prevention of serogroup B meningococcal disease has been challenged by researchers since Goldschneider et al. For 30 years. (Goldschneider et al., 1969, J. Exp. Med 129 (6): 1307-26; Goldschneider et al, 1969, J. Exp. Med 129 (6): 1327-48; Gotschlich et al., 1969, J Exp. Med. 129 (6): 1385-95; and Gotschlich et al., 1969, J. Exp. Med. 129 (6): 1367-84). Unlike serogroup A disease, which substantially disappeared from North America after the Second World War (Achtman, M., 1995, Trends in Microbiology 3 (5): 186-92), diseases caused by serogroup B and C organisms are developed economically. It is endemic throughout the world. The incidence of disease varies from less than 1 / 100,000, where endemic disease is rare, than 200 / 100,000 in high-risk individuals during epidemics.
[5] Vaccines based on polysaccharide conjugates are described in N. It has been developed for Meningitidis serogroups A and C and appears to be effective in the prevention of disease. Currently, immunogenic compositions consisting of capsular polysaccharides from serogroups A, C, Y, and W-135 are available (Ambrosch et al., 1983, Immunogenicity and side-effects of a new tetravalent. Bulletin of the World Health Organization 61 (2): 317-23). However, this immunogenic composition induces a T-cell independent immune response and is not effective for young children and does not provide coverage for serogroup B strains that cause more than 50% meningococcal disease.
[6] Other researchers are also trying to develop immunogenic compositions using capsular polysaccharides. Recently, immunogenic compositions for serogroup C disease prepared by conjugating serogroup C capsule material to proteins have been approved for use in Europe. However, serogroup B capsules may be inadequate as vaccine candidates because the capsular polysaccharide consists of polysialic acid with similarities to carbohydrate residues in human neural tissue development. These sugar residues are recognized as self-antigens and are therefore poor immunogenic in humans.
[7] Outer membrane protein (OMP) is being developed as another vaccine antigen for serogroup B disease. Monoclonal antibodies that bind the two variable regions of PorA define a serotype classification for meningococcal. Thus, PorA protein serves as a serotype subclass antigen for meningococcal strains (Abdillahi et al., 1988, Microbial Pathogenesis 4 (1): 27-32) and can induce bactericidal antibodies (Saukkonen, 1987, Microbial Pathogenesis 3 (4): 261-7) is actively investigated as a component of serogroup B immunogenic compositions (Poolman, 1996, Adv. Exp. Med. Biol. 397: 73-7). Bactericidal antibodies are considered as indicators of protection, and any novel immunogenic composition candidate should be able to induce these functional antibodies.
[8] Studies in animals as well as humans indicate that PorA, the serosubtype antigen, induces bactericidal antibodies. However, the immune response to PorA is generally serotype specific. In particular, the serotype classification data indicates that an immunogenic composition consisting of PorA may require as much as 6 to 9 PorA for each serotype comprised by such immunogenic composition. Thus, 6 to 9 PorAs will be needed to contain 70 to 80% serogroup B strains. Thus, the variable nature of this protein requires a multivalent vaccine composition to protect against a sufficient number of meningococcal serosubtype clinical isolates.
[9] The development of immunogenic compositions against serogroup B meningococcal has been difficult enough for recent groups to sequence genomes from strains representing both serogroups A and B to aid in identifying new immunogenic composition candidates (Tettelin, 2000, Science, 287). (5459): 1809-15; Pizza et al., 2000, Science 287: 1816-1820). The identification of new immunogenic composition candidates is a challenging method where no suitable mathematical algorithm currently exists, even with knowledge of the Neisseria genome. Indeed, recent reports, despite theoretically identifying 100 open reading frames ("ORFs") containing transmembrane domains, present problems with surface reactivity and the expression, purification and induction of functionally active antibodies in serogroup B meningococcal immunogenicity. Only seven candidates for the composition are shown to derive the investigator (reference Id). One of these is already known.
[10] Thus, (1) inducing bactericidal antibodies against multiple Neisseria strains; (2) react with the surface of multiple strains; (3) confer passive protection against surviving inoculum; (4) An immunogenic composition which prevents colonization is required.
[11] Summary of the Invention
[12] To meet these and other needs, and in view of its purpose, the present invention provides a Neisseria ORF2086 protein ("2086 protein") comprising a 2086 subfamily A protein and a 2086 subfamily B protein. Each of the 2086 proteins includes strains of Neisseria meningitidis (serum groups A, B, C, D, W-135, X, Y, Z and 29E), Neisseria gonorhoea, and Neisseria lactamica Is a protein that can be isolated from natural Neisseria strains. 2086 protein can also be prepared using recombinant techniques.
[13] In particular, the present invention provides a polynucleotide comprising a 2086 protein, an immunogenic portion thereof, and / or a biological equivalent thereof, an antibody immunospecifically binding to any of the above, and a nucleic acid sequence encoding any of the above. To provide. The present invention relates to compositions, immunogenic compositions and / or meningococcal infections, particularly N. a. Its use in the prophylaxis, treatment and / or diagnosis of meningococcal disease caused by meningitidis, as well as methods of preparing the compositions. The 2086 proteins herein include both recombinant and non-lipidized forms, as well as recombinant forms and forms isolated from natural sources.
[14] The present invention surprisingly and advantageously provides (1) many Neisseria strains, such as en. Meningitidis, N. Gonorhoea, and / or yen. Inducing bactericidal antibodies against strains of lactmica; (2) react with the surface of multiple strains; (3) confer passive protection against surviving inoculum; (4) Provided is a composition which prevents colonization, as well as a method of using the composition and a method of producing the composition. Various embodiments of the invention are described below.
[1] The present invention is directed to bacterial strains such as Neisseria meningitidis (serum groups A, B, C, D, W-135, X, Y, Z and 29E), Neisseria gonorrhoeae ), And Neisseria ORF2086 proteins (subfamily A and subfamily B) that can be isolated from those of Neisseria species, including strains of Neisseria lactamica, as well as immunogenic portions and / or of said proteins Relates to a biological equivalent. The present invention also relates to antibodies that immunospecifically bind to said proteins, immunogenic parts and / or biological equivalents. The invention also relates to an isolated polynucleotide comprising a nucleic acid sequence encoding any of the above proteins, immunogenic parts, biological equivalents and / or antibodies. In addition, the present invention is yen. Meningococcal infection caused by Meningitidis, in particular N. Immunogenic compositions and uses thereof, as well as methods for the prophylaxis, treatment and / or diagnosis of meningococcal disease caused by Meningitidis serogroup B. The present invention relates to both recombinant and non-lipidized forms, as well as recombinant forms and forms isolated from natural sources.
[15] 1A shows an SDS-PAGE gel showing two major proteins of the protein fraction obtained from experiments for the identification of Neisseria membrane protein extracts capable of inducing bactericidal antibodies against heterologous strains.
[16] 1B shows the results from experiments from the identification of two major proteins by TMAE Flow Through component analysis by protease cleavage and reversed phase N-terminal sequencing.
[17] 2 shows homogeneity measured by purification scheme and SDS-PAGE of rLP2086.
[18] 3 shows the results from experiments from the identification of two major proteins and one minor protein by TMAE flow through component analysis by LC-MS / MS and the corresponding SDS-PAGE.
[19] 4 is an SDS-PAGE gel from recombinant expression of 2086 protein.
[20] 5 is a schematic of plasmid pPX7340 described in the Examples herein.
[21] 6 is a schematic of plasmid pPX7328 as described in the Examples herein
[22] 7 is a schematic of plasmid pPX7343 described in the Examples herein
[23] 8 depicts the N-terminal region of the 2086 gene from various strains.
[24] 9A is a flow chart showing the preliminary steps in the identification of immunogenic components in Neisseria strains.
[25] 9B is a flow chart showing the final step in the identification of immunogenic components in Neisseria strains.
[26] 10A is a schematic of the pBAD arabinose inducible promoter that induces expression of the P4 signal / ORF2086 fusion protein to express the lipidated form of rP2086 described in the Examples herein.
[27] 1OB is a schematic of the pET9a-T7 vector for recombinant expression of the non-lipidated form of ORF2086.
[28] 11A shows E. coli expressing rLP2086 protein. Photograph showing the whole cell lysis of E. coli B.
[29] 11B shows E. coli expressing rP2086 protein. It is a photograph showing the whole cell fusion of E. coli B.
[30] 12 is a phylogenetic tree showing organization of subfamily and group of ORF2086 proteins.
[31] FIG. 13 is a graphical representation of whole cell ELISA data for rLP2086 subfamily A antiserum.
[32] 14 is a graphical representation of whole cell ELISA data for rLP2086 subfamily B antiserum.
[33] 15 is a graphical representation of the rLP2086 mixed study-WCE titer results.
[34] 16 is a graphical representation of the rLP2086 / rPorA mixing study-WCE titer results.
[35] 17 is P2086 subfamily B yen. Western blot showing the responsiveness of rLP2086 mouse antiserum to meningitidis whole cell lysis.
[36] 18 is P2086 subfamily A yen. Meningitidis and N. Western blot showing the reactivity of rLP2086 mouse antiserum to lactmica whole cell lysis.
[37] Sequence summary
[38] SEQ ID NO. For the sequence studied:
[39] SEQ NO: 1 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from L3 6275 strain when combined with a native leader sequence.
[40] SEQ NO: 2 amino acid sequence for mature 2086 protein from L3 6275 strain prepared using a native leader sequence.
[41] SEQ NO: 3 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from L3 6275 when combined with a P4 leader sequence.
[42] SEQ NO: 4: amino acid sequence for mature 2086 protein from L3 6275 strain prepared using a P4 leader sequence.
[43] SEQ NO: 5: nucleic acid sequence encoding amino acid sequence for mature 2086 protein from L3 6275 strain.
[44] SEQ NO: 6 amino acid sequence for mature 2086 protein from L3 6275 strain.
[45] SEQ NO: 7 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from CDC2369 strain when combined with a native leader sequence.
[46] SEQ NO: 8 amino acid sequence for mature 2086 protein from CDC2369 strain prepared using a native leader sequence.
[47] SEQ NO: 9 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from CDC2369 when combined with a P4 leader sequence.
[48] SEQ NO: 10 amino acid sequence for mature 2086 protein from CDC2369 strain prepared using a P4 leader sequence.
[49] SEQ NO: 11: nucleic acid sequence encoding amino acid sequence for mature 2086 protein from CDC2369 strain.
[50] SEQ NO: 12 amino acid sequence for mature 2086 protein from CDC2369 strain.
[51] SEQ NO: 13: nucleic acid sequence encoding amino acid sequence for mature 2086 protein from CDC1034 strain when combined with a native leader sequence.
[52] SEQ NO: 14 amino acid for mature 2086 protein from CDC1034 strain prepared using a native leader sequence.
[53] SEQ NO: 15 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from CDC1034 when combined with a P4 leader sequence.
[54] SEQ NO: 16: amino acid sequence for mature 2086 protein from CDC1034 strain prepared using a P4 leader sequence.
[55] SEQ NO: 17 nucleic acid sequence encoding amino acid for mature 2086 protein from CDC1034 strain.
[56] SEQ NO: 18 amino acid sequence for mature 2086 protein from CDC1034 strain.
[57] SEQ NO: 19 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from L4 891 strain when combined with a native leader sequence.
[58] SEQ NO: 20 amino acid sequence for mature 2086 protein from L4 891 strain prepared using a native leader sequence.
[59] SEQ NO: 21 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from L4 891 when combined with a P4 leader sequence.
[60] SEQ NO: 22 amino acid sequence for mature 2086 protein from L4 891 strain prepared using a P4 leader sequence.
[61] SEQ NO: 23 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from L4 891 strain.
[62] SEQ NO: 24 amino acid sequence for mature 2086 protein from L4 891 strain.
[63] SEQ NO: 25 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from B16B6 strain when combined with a native leader sequence.
[64] SEQ NO: 26 amino acid sequence for mature 2086 protein from B16B6 strain prepared using a native leader sequence.
[65] SEQ NO: 27 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from B16B6 when combined with a P4 leader sequence.
[66] SEQ NO: 28 amino acid sequence for mature 2086 protein from B16B6 strain prepared using a P4 leader sequence.
[67] SEQ NO: 29 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from B16B6 strain.
[68] SEQ NO: 30 amino acid sequence for mature 2086 protein from B16B6 strain.
[69] SEQ NO: 31 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from W135 (ATCC35559) strain when combined with a native leader sequence.
[70] SEQ NO: 32 amino acid sequence for mature 2086 protein from W135 (ATCC35559) strain prepared using a native leader sequence.
[71] SEQ NO: 33 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from W135 (ATCC35559) when combined with a P4 leader sequence.
[72] SEQ NO: 34 amino acid sequence for mature 2086 protein from W135 (ATCC35559) strain prepared using a P4 leader sequence.
[73] SEQ NO: 35 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from W135 (ATCC35559) strain.
[74] SEQ NO: 36 amino acid sequence for mature 2086 protein from W135 (ATCC35559) strain.
[75] SEQ NO: 37 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from C11 strain when combined with a native leader sequence.
[76] SEQ NO: 38 amino acid sequence for mature 2086 protein from C11 strain prepared using a native leader sequence.
[77] SEQ NO: 39 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from C11 when combined with a P4 leader sequence.
[78] SEQ NO: 40 amino acid sequence for mature 2086 protein from C11 strain prepared using a P4 leader sequence.
[79] SEQ NO: 41 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from C11 strain.
[80] SEQ NO: 42 amino acid sequence for mature 2086 protein from C11 strain.
[81] SEQ NO: 43 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from Y (ATCC35561) strain when combined with a native leader sequence.
[82] SEQ NO: 44 amino acid sequence for mature 2086 protein from Y (ATCC35561) strain prepared using a native leader sequence.
[83] SEQ NO: 45 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from Y (ATCC35561) when combined with a P4 leader sequence.
[84] SEQ NO: 46 amino acid sequence for mature 2086 protein from Y (ATCC35561) strain prepared using a P4 leader sequence.
[85] SEQ NO: 47 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from Y (ATCC35561) strain.
[86] SEQ NO: 48 amino acid sequence for mature 2086 protein from Y (ATCC35561) strain.
[87] SEQ NO: 49 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from M98 250732 strain when combined with a native leader sequence.
[88] SEQ NO: 50 amino acid sequence for mature 2086 protein from M98 250732 strain prepared using a native leader sequence.
[89] SEQ NO: 51 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M98 250732 when combined with a P4 leader sequence.
[90] SEQ NO: 52 amino acid sequence for mature 2086 protein from M98 250732 strain prepared using a P4 leader sequence.
[91] SEQ NO: 53 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from M98 250732 strain.
[92] SEQ NO: 54 amino acid sequence for mature 2086 protein from M98 250732 strain.
[93] SEQ NO: 55 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from M98 250771 strain when combined with a native leader sequence.
[94] SEQ NO: 56 amino acid sequence for mature 2086 protein from M98 250771 strain prepared using a native leader sequence.
[95] SEQ NO: 57 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M98 250771 when combined with a P4 leader sequence.
[96] SEQ NO: 58 amino acid sequence for mature 2086 protein from M98 250771 strain prepared using a P4 leader sequence.
[97] SEQ NO: 59 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from M98 250771 strain.
[98] SEQ NO: 60 amino acid sequence for mature 2086 protein from M98 250771 strain.
[99] SEQ NO: 61 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from CDC1135 strain when combined with a native leader sequence.
[100] SEQ NO: 62 amino acid sequence for mature 2086 protein from CDC1135 strain prepared using a native leader sequence.
[101] SEQ NO: 63 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from CDC1135 when combined with a P4 leader sequence.
[102] SEQ NO: 64 amino acid sequence for mature 2086 protein from CDC1135 strain prepared using a P4 leader sequence.
[103] SEQ NO: 65 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from CDC1135 strain.
[104] SEQ NO: 66 amino acid sequence for mature 2086 protein from CDC1135 strain.
[105] SEQ NO: 67 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M97 252153 strain when combined with a native leader sequence.
[106] SEQ NO: 68 amino acid sequence for mature 2086 protein from M97 252153 strain prepared using a native leader sequence.
[107] SEQ NO: 69 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M97 252153 when combined with a P4 leader sequence.
[108] SEQ NO: 70 amino acid sequence for mature 2086 protein prepared using a P4 leader sequence from a M97 252153 strain.
[109] SEQ NO: 71 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from M97 252153 strain.
[110] SEQ NO: 72 amino acid sequence for mature 2086 protein from M97 252153 strain.
[111] SEQ NO: 73 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from CDC1610 strain when combined with a native leader sequence.
[112] SEQ NO: 74 amino acid sequence for mature 2086 protein from CDC1610 strain prepared using a native leader sequence.
[113] SEQ NO: 75 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from CDC1610 when combined with a P4 leader sequence.
[114] SEQ NO: 76 amino acid sequence for mature 2086 protein from CDC1610 strain prepared using a P4 leader sequence.
[115] SEQ NO: 77 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from CDC1610 strain.
[116] SEQ NO: 78 amino acid sequence for mature 2086 protein from CDC1610 strain.
[117] SEQ NO: 79 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from CDC1492 strain when combined with a native leader sequence.
[118] SEQ NO: 80 amino acid sequence for mature 2086 protein from CDC1492 strain prepared using a native leader sequence.
[119] SEQ NO: 81 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from CDC1492 when combined with a P4 leader sequence.
[120] SEQ NO: 82 amino acid sequence for mature 2086 protein from CDC1492 strain prepared using a P4 leader sequence.
[121] SEQ NO: 83 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from CDC1492 strain.
[122] SEQ NO: 84 amino acid sequence for mature 2086 protein from CDC1492 strain.
[123] SEQ NO: 85 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from L8 M978 strain when combined with a native leader sequence.
[124] SEQ NO: 86 amino acid sequence for mature 2086 protein from L8 M978 strain prepared using a native leader sequence.
[125] SEQ NO: 87 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from L8 M978 when combined with a P4 leader sequence.
[126] SEQ NO: 88 amino acid sequence for mature 2086 protein from L8 M978 strain prepared using a P4 leader sequence.
[127] SEQ NO: 89 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from L8 M978 strain.
[128] SEQ NO: 90 amino acid sequence for mature 2086 protein from L8 M978 strain.
[129] SEQ NO: 91 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M97 252988 strain when combined with a native leader sequence.
[130] SEQ NO: 92 amino acid sequence for mature 2086 protein from M97 252988 strain prepared using a native leader sequence.
[131] SEQ NO: 93 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M97 252988 when combined with a P4 leader sequence.
[132] SEQ NO: 94 amino acid sequence for mature 2086 protein from M97 252988 strain prepared using a P4 leader sequence.
[133] SEQ NO: 95 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from M97 252988 strain.
[134] SEQ NO: 96 amino acid sequence for mature 2086 protein from M97 252988 strain.
[135] SEQ NO: 97 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M97 252697 strain when combined with a native leader sequence.
[136] SEQ NO: 98 amino acid sequence for mature 2086 protein from M97 252697 strain prepared using a native leader sequence.
[137] SEQ NO: 99 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M97 252697 when combined with a P4 leader sequence.
[138] SEQ NO: 100 amino acid sequence for mature 2086 protein from M97 252697 strain prepared using a P4 leader sequence.
[139] SEQ NO: 101 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from M97 252697 strain.
[140] SEQ NO: 102 amino acid sequence for mature 2086 protein from M97 252697 strain.
[141] SEQ NO: 103 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from 6557 strain when combined with a native leader sequence.
[142] SEQ NO: 104 amino acid sequence for mature 2086 protein from 6557 strain prepared using a native leader sequence.
[143] SEQ NO: 105 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from 6557 when combined with a P4 leader sequence.
[144] SEQ NO: 106 amino acid sequence for mature 2086 protein from 6557 strain prepared using a P4 leader sequence.
[145] SEQ NO: 107 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from 6557 strain.
[146] SEQ NO: 108 amino acid sequence for mature 2086 protein from 6557 strain.
[147] SEQ NO: 109 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from 2996 strain when combined with a native leader sequence.
[148] SEQ NO: 110 amino acid sequence for mature 2086 protein from 2996 strain prepared using a native leader sequence.
[149] SEQ NO: 111 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from 2996 when combined with a P4 leader sequence.
[150] SEQ NO: 112 amino acid sequence for mature 2086 protein from 2996 strain prepared using a P4 leader sequence.
[151] SEQ NO: 113 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from 2996 strain.
[152] SEQ NO: 114 amino acid sequence for mature 2086 protein from 2996 strain.
[153] SEQ NO: 115 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M97 252976 strain when combined with a native leader sequence.
[154] SEQ NO: 116 amino acid sequence for mature 2086 protein from M97 252976 strain prepared using a native leader sequence.
[155] SEQ NO: 117 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M97 252976 when combined with a P4 leader sequence.
[156] SEQ NO: 118 amino acid sequence for mature 2086 protein from M97 252976 strain prepared using a P4 leader sequence.
[157] SEQ NO: 119 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from M97 252976 strain.
[158] SEQ NO: 120 amino acid sequence for mature 2086 protein from M97 252976 strain.
[159] SEQ NO: 121 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M97 251854 strain when combined with a native leader sequence.
[160] SEQ NO: 122 amino acid sequence for mature 2086 protein from M97 251854 strain prepared using a native leader sequence.
[161] SEQ NO: 123 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M97 251854 when combined with a P4 leader sequence.
[162] SEQ NO: 124 amino acid sequence for mature 2086 protein from M97 251854 strain prepared using a P4 leader sequence.
[163] SEQ NO: 125 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from M97 251854 strain.
[164] SEQ NO: 126 amino acid sequence for mature 2086 protein from M97 251854 strain.
[165] SEQ NO: 127 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from CDC1521 strain when combined with a native leader sequence.
[166] SEQ NO: 128 amino acid sequence for mature 2086 protein from CDC1521 strain prepared using a native leader sequence.
[167] SEQ NO: 129 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from CDC1521 when combined with a P4 leader sequence.
[168] SEQ NO: 130 amino acid sequence for mature 2086 protein from CDC1521 strain prepared using a P4 leader sequence.
[169] SEQ NO: 131 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from CDC1521 strain.
[170] SEQ NO: 132 amino acid sequence for mature 2086 protein from CDC1521 strain.
[171] SEQ NO: 133 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M98 250622 strain when combined with a native leader sequence.
[172] SEQ NO: 134 amino acid sequence for mature 2086 protein from M98 250622 strain prepared using a native leader sequence.
[173] SEQ NO: 135 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M98 250622 when combined with a P4 leader sequence.
[174] SEQ NO: 136 amino acid sequence for mature 2086 protein from M98 250622 strain prepared using a P4 leader sequence.
[175] SEQ NO: 137 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from M98 250622 strain.
[176] SEQ NO: 138 amino acid sequence for mature 2086 protein from M98 250622 strain.
[177] SEQ NO: 139 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from 870446 strain when combined with a native leader sequence.
[178] SEQ NO: 140 amino acid sequence for mature 2086 protein from 870446 strain prepared using a native leader sequence.
[179] SEQ NO: 141 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from 870446 when combined with a P4 leader sequence.
[180] SEQ NO: 142 amino acid sequence for mature 2086 protein from 870446 strain prepared using a P4 leader sequence.
[181] SEQ NO: 143 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from 870446 strain.
[182] SEQ NO: 144 amino acid sequence for mature 2086 protein from 870446 strain.
[183] SEQ NO: 145 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M97 253248 strain when combined with a native leader sequence.
[184] SEQ NO: 146 amino acid sequence for mature 2086 protein from M97 253248 strain prepared using a native leader sequence.
[185] SEQ NO: 147 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M97 253248 when combined with a P4 leader sequence.
[186] SEQ NO: 148 amino acid sequence for mature 2086 protein from M97 253248 strain prepared using a P4 leader sequence.
[187] SEQ NO: 149 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from M97 253248 strain.
[188] SEQ NO: 150 amino acid sequence for mature 2086 protein from M97 253248 strain.
[189] SEQ NO: 151 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M98 250809 strain when combined with a native leader sequence.
[190] SEQ NO: 152 amino acid sequence for mature 2086 protein from M98 250809 strain prepared using a native leader sequence.
[191] SEQ NO: 153 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M98 250809 when combined with a P4 leader sequence.
[192] SEQ NO: 154 amino acid sequence for mature 2086 protein from M98 250809 strain prepared using a P4 leader sequence.
[193] SEQ NO: 155 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from M98 250809 strain.
[194] SEQ NO: 156 amino acid sequence for mature 2086 protein from M98 250809 strain.
[195] SEQ NO: 157 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from L5 M981 strain when combined with a native leader sequence.
[196] SEQ NO: 158 amino acid sequence for mature 2086 protein from L5 M981 strain prepared using a native leader sequence.
[197] SEQ NO: 159 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from L5 M981 when combined with a P4 leader sequence.
[198] SEQ NO: 160 amino acid sequence for mature 2086 protein from L5 M981 strain prepared using a P4 leader sequence.
[199] SEQ NO: 161 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from L5 M981 strain.
[200] SEQ NO: 162 amino acid sequence for mature 2086 protein from L5 M981 strain.
[201] SEQ NO: 163 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from NMB strain when combined with a native leader sequence.
[202] SEQ NO: 164 amino acid sequence for mature 2086 protein from NMB strain prepared using a native leader sequence.
[203] SEQ NO: 165 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from NMB when combined with a P4 leader sequence.
[204] SEQ NO: 166 amino acid sequence for mature 2086 protein from NMB strain prepared using a P4 leader sequence.
[205] SEQ NO: 167 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from NMB strain.
[206] SEQ NO: 168 amino acid sequence for mature 2086 protein from NMB strain.
[207] SEQ NO: 169 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from M98 250572 strain when combined with a native leader sequence.
[208] SEQ NO: 170 amino acid sequence for mature 2086 protein from M98 250572 strain prepared using a native leader sequence.
[209] SEQ NO: 171 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M98 250572 when combined with a P4 leader sequence.
[210] SEQ NO: 172 amino acid sequence for mature 2086 protein from M98 250572 strain prepared using a P4 leader sequence.
[211] SEQ NO: 173 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from M98 250572 strain.
[212] SEQ NO: 174 amino acid sequence for mature 2086 protein from M98 250572 strain.
[213] SEQ NO: 175 A4 Sanford in combination with native leader sequence; M97 251836 PART; M97 251957; M97 251985; M97 252060; M97 251870; M97 251994; M98 250024; M97 251905; M97 251876; M97 251898; Or a nucleic acid sequence encoding an amino acid sequence for mature 2086 protein from M97 251830 strain.
[214] SEQ NO: 176 A4 sanford prepared using a native leader sequence; M97 251836 PART; M97 251957; M97 251985; M97 252060; M97 251870; M97 251994; M98 250024; M97 251905; M97 251876; M97 251898; Or the amino acid sequence for mature 2086 protein from M97 251830 strain.
[215] SEQ NO: 177 A4 sanford when combined with a P4 leader sequence; M97 251836 PART; M97 251957; M97 251985; M97 252060; M97 251870; M97 251994; M98 250024; M97 251905; M97 251876; M97 251898; Or a nucleic acid sequence for encoding an amino acid sequence for mature 2086 protein from M97 251830.
[216] SEQ ID NO: 178 A4 sanford; M97 251836 PART; M97 251957; M97 251985; M97 252060; M97 251870; M97 251994; M98 250024; M97 251905; M97 251876; M97 251898; Or the amino acid sequence for mature 2086 protein prepared using a P4 leader sequence from the M97 251830 strain.
[217] SEQ NO: 179 A4 sanford; M97 251836 PART; M97 251957; M97 251985; M97 252060; M97 251870; M97 251994; M98 250024; M97 251905; M97 251876; M97 251898; Or a nucleic acid sequence encoding an amino acid sequence for mature 2086 protein from M97 251830 strain.
[218] SEQ ID NO: 180: A4 sanford; M97 251836 PART; M97 251957; M97 251985; M97 252060; M97 251870; M97 251994; M98 250024; M97 251905; M97 251876; M97 251898; Or the amino acid sequence for mature 2086 protein from M97 251830 strain.
[219] SEQ NO: 181 nucleic acid sequence encoding partial amino acid sequence for mature 2086 protein from CDC937 strain when combined with a native leader sequence.
[220] SEQ NO: 182 amino acid sequence for mature 2086 protein from CDC937 strain prepared using a native leader sequence.
[221] SEQ NO: 183 nucleic acid sequence for encoding partial amino acid sequence for mature 2086 protein from CDC937 when combined with a P4 leader sequence.
[222] SEQ NO: 184 amino acid sequence for mature 2086 protein from CDC937 strain prepared using a P4 leader sequence.
[223] SEQ NO: 185 nucleic acid sequence encoding partial amino acid sequence for mature 2086 protein from CDC937 strain.
[224] SEQ NO: 186 amino acid sequence for mature 2086 protein from CDC937 strain.
[225] SEQ NO: 187 nucleic acid sequence encoding partial amino acid sequence for mature 2086 protein from M97 252097 strain when combined with a native leader sequence.
[226] SEQ NO: 188 amino acid sequence for mature 2086 protein from M97 252097 strain prepared using a native leader sequence.
[227] SEQ NO: 189 nucleic acid sequence for encoding partial amino acid sequence for mature 2086 protein from M97 252097 when combined with a P4 leader sequence.
[228] SEQ NO: 190 amino acid sequence for mature 2086 protein from M97 252097 strain prepared using a P4 leader sequence.
[229] SEQ NO: 191 nucleic acid sequence encoding partial amino acid sequence for mature 2086 protein from M97 252097 strain.
[230] SEQ NO: 192 amino acid sequence for mature 2086 protein from M97 252097 strain.
[231] SEQ NO: 193 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from 870227 strain when combined with a native leader sequence.
[232] SEQ NO: 194 amino acid sequence for mature 2086 protein from 870227 strain prepared using a native leader sequence.
[233] SEQ NO: 195 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from 870227 when combined with a P4 leader sequence.
[234] SEQ NO: 196 amino acid sequence for mature 2086 protein from 870227 strain prepared using a P4 leader sequence.
[235] SEQ NO: 197 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from 870227 strain.
[236] SEQ NO: 198 amino acid sequence for mature 2086 protein from 870227 strain.
[237] SEQ NO: 199 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from H355 strain when combined with a native leader sequence.
[238] SEQ NO: 200 amino acid sequence for mature 2086 protein from H355 strain prepared using a native leader sequence.
[239] SEQ NO: 201 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from H355 when combined with a P4 leader sequence.
[240] SEQ NO: 202 amino acid sequence for mature 2086 protein from H355 strain prepared using a P4 leader sequence.
[241] SEQ NO: 203 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from H355 strain.
[242] SEQ NO: 204 amino acid sequence for mature 2086 protein from H355 strain.
[243] SEQ NO: 205 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from H4476 strain when combined with a native leader sequence.
[244] SEQ NO: 206 amino acid sequence for mature 2086 protein from H4476 strain prepared using a native leader sequence.
[245] SEQ NO: 207 amino acid sequence for mature 2086 protein from H4476 strain prepared using a P4 leader sequence.
[246] SEQ NO: 208 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from H4476 strain.
[247] SEQ NO: 209 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from H4476 when combined with a P4 leader sequence.
[248] SEQ NO: 210 amino acid sequence for mature 2086 protein from H4476 strain.
[249] SEQ NO: 211 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from 8529 strain when combined with a native leader sequence.
[250] SEQ NO: 212 amino acid sequence for mature 2086 protein from 8529 strain prepared using a native leader sequence.
[251] SEQ NO: 213 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from 8529 when combined with a P4 leader sequence.
[252] SEQ NO: 214 amino acid sequence for mature 2086 protein from 8529 strain prepared using a P4 leader sequence.
[253] SEQ NO: 215 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from 8529 strain.
[254] SEQ NO: 216 amino acid sequence for mature 2086 protein from 8529 strain.
[255] SEQ NO: 217 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from 6940 strain when combined with a native leader sequence.
[256] SEQ NO: 218 amino acid sequence for mature 2086 protein from 6940 strain prepared using a native leader sequence.
[257] SEQ NO: 219 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from 6940 when combined with a P4 leader sequence.
[258] SEQ NO: 220 amino acid sequence for mature 2086 protein from 6940 strain prepared using a P4 leader sequence.
[259] SEQ NO: 221 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from 6940 strain.
[260] SEQ NO: 222 amino acid sequence for mature 2086 protein from 6940 strain.
[261] SEQ NO: 223 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M982 strain when combined with a native leader sequence.
[262] SEQ NO: 224 amino acid sequence for mature 2086 protein from M982 strain prepared using a native leader sequence.
[263] SEQ NO: 225 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M982 when combined with a P4 leader sequence.
[264] SEQ NO: 226 amino acid sequence for mature 2086 protein from M982 strain prepared using a P4 leader sequence.
[265] SEQ NO: 227 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from M982 strain.
[266] SEQ NO: 228 amino acid sequence for mature 2086 protein from M982 strain.
[267] SEQ NO: 229 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from 880049 strain when combined with a native leader sequence.
[268] SEQ NO: 230 amino acid sequence for mature 2086 protein from 880049 strain prepared using a native leader sequence.
[269] SEQ NO: 231 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from 880049 when combined with a P4 leader sequence.
[270] SEQ NO: 232 amino acid sequence for mature 2086 protein from 880049 strain prepared using a P4 leader sequence.
[271] SEQ NO: 233 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from 880049 strain.
[272] SEQ NO: 234 amino acid sequence for mature 2086 protein from 880049 strain.
[273] SEQ NO: 235 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from M97 253524, M97 251885, and M97 251926 strains when combined with a native leader sequence.
[274] SEQ NO: 236 amino acid sequence for mature 2086 protein from M97 253524, M97 251885, and M97 251926 strains prepared using a native leader sequence.
[275] SEQ NO: 237 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M97 253524, M97 251885, and M97 251926 strains when combined with a P4 leader sequence.
[276] SEQ NO: 238 amino acid sequence for mature 2086 protein from M97 253524, M97 251885, and M97 251926 strains prepared using a P4 leader sequence.
[277] SEQ NO: 239 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from M97 253524, M97 251885, and M97 251926 strains.
[278] SEQ NO: 240 amino acid sequence for mature 2086 protein from M97 253524, M97 251885, and M97 251926 strains.
[279] SEQ NO: 241 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M98 250670 strain when combined with a native leader sequence.
[280] SEQ NO: 242 amino acid sequence for mature 2086 protein from M98 250670 strain prepared using a native leader sequence.
[281] SEQ NO: 243 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from M98 250670 when combined with a P4 leader sequence.
[282] SEQ NO: 244 amino acid sequence for mature 2086 protein from M98 250670 strain prepared using a P4 leader sequence.
[283] SEQ NO: 245 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from M98 250670 strain.
[284] SEQ NO: 246 amino acid sequence for mature 2086 protein from M98 250670 strain.
[285] SEQ NO: 247 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from CDC1573 strain when combined with a native leader sequence.
[286] SEQ NO: 248 amino acid sequence for mature 2086 protein from CDC1573 strain prepared using a native leader sequence.
[287] SEQ NO: 249 nucleic acid sequence for encoding amino acid sequence for mature 2086 protein from CDC1573 when combined with a P4 leader sequence.
[288] SEQ NO: 250 amino acid sequence for mature 2086 protein from CDC1573 strain prepared using a P4 leader sequence.
[289] SEQ NO: 251 nucleic acid sequence encoding amino acid sequence for mature 2086 protein from CDC1573 strain.
[290] SEQ NO: 252 amino acid sequence for mature 2086 protein from CDC1573 strain.
[291] SEQ NO: 253 partial nucleic acid sequence for encoding amino acid sequence for 2086 protein from Neisseria lactamica strain.
[292] SEQ NO: 254 to 259: amino acid sequence associated with a protein of the 2086 protein family.
[293] SEQ ID NOs: 260 to 278: 2086 amino acid sequence linked to protein subfamily A.
[294] SEQ ID NOs: 279 to 299: amino acid sequence linked to 2086 protein subfamily B.
[295] SEQ NO: 300 amino acid consensus sequence corresponding to 2086 protein family ("2086 protein") according to an embodiment of the present invention.
[296] SEQ NO: 301 amino acid consensus sequence corresponding to 2086 protein subfamily A according to an embodiment of the invention.
[297] SEQ NO: 302 amino acid consensus sequence corresponding to 2086 protein subfamily B according to an embodiment of the invention.
[298] SEQ NO: 303 nucleic acid sequence for reverse primer having BamHI restriction enzyme cleavage site (Compound No. 4623).
[299] SEQ NO: 304 nucleic acid sequence for forward primer having a NdeI restriction site (compound number 4624).
[300] SEQ NO: 305 nucleic acid sequence for a forward primer (Compound No. 4625).
[301] SEQ NO: 306 nucleic acid sequence for a forward primer (Compound No. 5005).
[302] SEQ NO: 307 nucleic acid sequence for a reverse primer (Compound No. 5007).
[303] SEQ NO: 308 nucleic acid sequence for reverse primer having BglII restriction enzyme cleavage site (Compound No. 5135).
[304] SEQ NO: 309 nucleic acid sequence for forward primer having a BamHI restriction site (Compound No. 5658).
[305] SEQ NO: 310 nucleic acid sequence for a reverse primer having a SphI restriction enzyme cleavage site (Compound No. 5660).
[306] SEQ NO: 311 nucleic acid sequence for forward primer having a BamHI restriction site (Compound No. 6385).
[307] SEQ NO: 312 nucleic acid sequence for forward primer having a BglII and NdeI restriction site (Compound No. 6406).
[308] SEQ NO: 313 nucleic acid sequence for a forward primer (Compound No. 6470).
[309] SEQ NO: 314 nucleic acid sequence for reverse primer (Compound No. 6472).
[310] SEQ NO: 315 nucleic acid sequence for forward primer having a BamHI restriction site (compound 6473).
[311] SEQ NO: 316 nucleic acid sequence for forward primer having a BglII and NdeI restrictionase cleavage site (Compound No. 6474).
[312] SEQ NO: 317 nucleic acid sequence for a forward primer (Compound No. 6495).
[313] SEQ NO: 318 nucleic acid sequence for a reverse primer (Compound No. 6496).
[314] SEQ NO: 319 nucleic acid sequence for reverse primer having SphI restriction enzyme cleavage site (Compound No. 6543).
[315] SEQ NO: 320 nucleic acid sequence for reverse primer having BglII restriction enzyme cleavage site (Compound No. 6605).
[316] SEQ NO: 321 nucleic acid sequence for forward primer with BglII and NdeI restriction enzyme cleavage site (Compound No. 6721).
[317] SEQ NO: 322 nucleic acid sequence for P4 leader sequence.
[318] SEQ NO: 323 nucleic acid sequence for native 2086 leader modification 1.
[319] SEQ NO: 324 nucleic acid sequence for native 2086 leader modification 2.
[320] SEQ NO: 325 nucleic acid sequence for native 2086 leader modification 3.
[321] SEQ NO: 326 nucleic acid sequence for native 2086 leader modification 4.
[322] SEQ NO: 327 amino acid sequence of P4431.
[323] SEQ NO: 328 amino acid sequence of P5163.
[324] SEQ NO: 329 amino acid sequence according to an embodiment of the present invention.
[325] A new class of antigens with cross-functional bactericidal activity against Neisseria meningitidis serogroup B will obviate the need for a multivalent PorA study of immunization against infection. Such antigens are unexpectedly identified and described and claimed herein. The presence of one such antigen was first observed in a complex mixture of soluble outer membrane proteins (sOMPs) from meningococcal strains. The bactericidal activity of this antigen was obtained through a series of fractionation and protein purification steps until the desired protein mixture contains only a few proteins. Major proteins in this mixture were identified by N-terminal amino acid sequencing and peptide mapping. The protein of interest showing bactericidal activity has been identified as the lipidated protein ORF2086 protein (more particularly also referred to as LP2086). "ORF2086 protein" refers to a protein encoded by an open reading frame 2086 (ORF2086) of a Neisseria species.
[326] As described herein, N. Neisseria spp. ORF2086 protein isolated from Meningitidis (also referred to as "2086 protein" or "ORF2086" protein (used interchangeably herein)), or for non-lipidated proteins for lipidated modification of P2086 and proteins New immunogenic composition candidates, also referred to as LP2086, were identified by combining cell fractionation, differential detergent extraction, protein purification, and bactericidal activity assays using multiple strains with the preparation of antiserum. As an alternative to the potent immunogenic compositions and diagnostics disclosed in the references cited above, the present invention relates to proteins, immunogenic portions and biological equivalents thereof, as well as genes encoding such polypeptides, portions and equivalents, and to the same. The present invention relates to compositions and methods for treating and / or preventing meningococcal infection using immunospecifically binding antibodies.
[327] According to an embodiment of the present invention, an immunogenic agent based on a 2086 protein comprising an isolated polypeptide, an immunogenic portion thereof and / or a biological equivalent thereof may be prepared by any of the above agents exhibiting cross-reactive or non-strain specificity. It was unexpectedly identified as an immunogenic candidate on the basis of ability. In particular, (1) induces bactericidal antibodies against a number of Neisseria and / or gonococci strains; (2) react with the surface of multiple strains; (3) confer passive protection against surviving inoculum; (4) I identified a candidate who unexpectedly showed his ability to prevent colonization. Accordingly, the present invention relates to immunogenic compositions, as well as to immunogenic agents, comprising an isolated polypeptide, an immunogenic portion thereof, and / or a biological equivalent thereof. Provided are methods of using the same for infection with meningitidis (see Example 1 herein for the method used for identification of 2086 protein).
[328] As used herein, the term “non-strain specificity” refers to en. Refers to the characteristics of antigens that elicit an effective immune response against one or more strains of meningitidis (eg, heterologous meningococcal strains). As used herein, the term "cross-reactivity" is used interchangeably with the term "non-strain specificity". As used herein, the term “immunogenic non-strain specific N. meningitidis antigen” is defined as N. a. It is intended to describe antigens that can be isolated from meningitidis but can be isolated from another bacterium (eg, other Neisseria strains, such as gonococcus strains) or prepared using recombinant techniques.
[329] 2086 proteins of the invention include lipidized and non-lipidated proteins. The present invention also contemplates the use of immature proteins or shear proteins corresponding to each protein as intermediate compounds / compositions.
[330] The invention also provides antibodies that immunospecifically bind to said immunogenic agents in accordance with the practice of the invention. The invention also relates to an isolated polynucleotide comprising a nucleic acid sequence encoding any of the above. The present invention also provides compositions and / or immunogenic compositions and uses thereof in the prevention, treatment and / or diagnosis of meningococcal meningitis, in particular serogroup B meningococcal disease, as well as methods of making such compositions.
[331] The compositions of the present invention have been shown to be highly immunogenic and capable of inducing sterile antibody production. These antibodies are cross-reactive with serogroup, serotype and serosubtype heterologous meningococcal strains. Thus, the composition exhibits the ability to induce bactericidal antibodies against heterologous Neisseria strains. Overcome the lack of Meningitidis vaccine attempts. Thus, among other advantages, the present invention provides immunogenic compositions that can be combined with fewer ingredients to induce protection comparable to previously used formulations. The compositions or immunogenic agents herein (eg, but not limited to, polypeptides, immunogenic parts or fragments, and biological equivalents) may be used alone or in other antigens or agents that induce immunological protection from meningococcal infections and diseases. As well as other antigens or agents that induce immunological protection from infections and / or diseases caused by other pathogens. This simplifies the design of immunogenic compositions for use against meningococcal infection by reducing the number of antigens required for protection against many strains. In fact, purified 2086 protein will dramatically and unexpectedly reduce the number of proteins required to provide adequate immunogenic coverage of the strains responsible for meningococcal disease. 2086 protein is this. In E. coli can be expressed recombinantly as a lipoprotein that is a wild type of protein at a higher level than native meningococcal.
[332] Since related antibodies to 2086 protein against a single strain have been found to kill irrelevant (ie heterologous) strains, several attempts have been made to characterize multiple heterologous strains for the presence of the "2086 homologue" and to determine the sequence conservation level. . About 70% of the strains tested by PCR had 2086 homologues that could be amplified using primers that amplify the original 2086 gene from strain 8529, while about 30% of the remaining were negative by this test. About 30% of these residues were found to include 2086 homologues with only about 60% amino acid sequence homology to the original 8529 derived 2086 gene. Other primers have been identified that can amplify 2086 homologues from about 30% of these strains. Yen tested. Meningitidis strains were designed to belong to subfamily A or subfamily B, as the primer set was able to amplify 2086 homologues. Details of these experiments are outlined in Example 5 below.
[333] The presence of 2086 protein in many serotypes.
[334] yen. Several representatives from subfamily A and B were cloned as full length genes and DNA sequence analyzed to determine the sequence conservation level of the 2086 gene between Meningitidis strains. Using the primers described herein (see, eg, Table 4), 24 serogroup B meningococcal strains were identified, different serotype antigens were expressed, and also the covalent protein P2086. Examples of these sequences are provided herein and are shown as mature DNA sequences (ie, all lipoprotein signal sequences have been cleaved at cysteine residues) (eg, amino acid sequences of even sequences in SEQ ID NOs: 2-252, without limitation) .
[335] Although the 2086 protein is not present in large amounts in wild type strains, it is a target for sterile antibodies. Unlike those produced in response to PorA, these antibodies can kill strains that express heterologous serotypes.
[336] Antibodies to the 2086 protein also passively protect pups from inoculation with meningococcal (see Table 7). Recombinant expression of the 2086 protein may result in the use of the 2086 protein as an immunogenic composition for meningococcal disease prevention. In clinical trials all of the recent meningococcal immunogenic composition candidates were complex mixtures or envelope protein preparations containing many different proteins. PorA proteins that provide serosubtype specificity will require the inclusion of 6 to 9 variants in immunogenic compositions that provide about 70 to 80% coverage of disease related serotypes. In contrast, it is clearly shown that antisera alone against a single 2086 protein can kill six representative serosubtypes for about 65% of diseases isolated in Western Europe and the United States. Thus, purified 2086 protein has the potential to reduce the number of protein species required to provide adequate immunogenic composition coverage of serotypes against meningococcal disease.
[337] Proteins, immunogenic parts and biological equivalents
[338] The 2086 protein provided by the present invention is an isolated protein. The term "isolated" means altered by the human hand from its natural state. When an "isolated" composition or material occurs in nature, the composition or material has changed or removed from its original environment, or both. For example, a polypeptide or polynucleotide that is naturally present in a living animal is the term "isolated" as used herein, while the same polypeptide or polynucleotide isolated from its natural coexistent material is "isolated". Thus, as used herein, the term “isolated protein” refers to proteins isolated from natural sources and proteins prepared using recombinant techniques, as well as other antigens and / or additives such as pharmaceutically acceptable carriers, buffers. And such proteins in combination with adjuvant, and the like.
[339] 2086 protein, immunogenic portion thereof and / or biological equivalent thereof according to an embodiment of the present invention comprises any of the following amino acid sequences:
[340]
[341] According to an embodiment of the invention the 2086 subfamily A protein, immunogenic portion thereof and / or biological equivalent thereof comprises any of the following amino acid sequences:
[342]
[343]
[344] According to an embodiment of the invention the 2086 subfamily B protein, its immunogenic portion and / or its biological equivalent comprises any of the following amino acid sequences:
[345]
[346]
[347] According to an embodiment of the invention the 2086 protein comprises the following consensus sequence and / or immunogenic portion thereof.
[348] 2086 protein consensus sequence (SEQ ID NO: 300):
[349]
[350] In the consensus sequence, “x” represents any amino acid, the region at amino acid position 5 to amino acid position 9 is any 0 to 5 amino acids, and the region at amino acid position 67 to amino acid position 69 is any 0 to 3 amino acids. Amino acid, and amino acid position 156 is any 0 to 1 amino acid. The region of amino acid position 5 to amino acid position 9 preferably comprises 0, 4 or 5 amino acids. The region of amino acid position 67 to amino acid position 69 preferably comprises 0 or 3 amino acids. It should be particularly noted that this consensus sequence exhibits high variability of the 2086 protein. Theoretically, this high variability is believed to provide advantageous and unexpected cross-reactivity without the purpose of being bound thereto.
[351] In accordance with the practice of the present invention, 2086 protein is characterized for immunogenicity, non-pathogenicity and non-strain specificity. In addition, according to a further implementation of the invention these proteins are unexpectedly immunogenic while being about 2% to about 40% nonconserved.
[352] As used herein, the term “non-conserved” refers to the number of amino acids in which insertions, substitutions, and / or deletions can occur as a percentage of the total number of amino acids in the protein. For example, if a protein is 40% unconserved and has 263 amino acids, for example, there are 105 amino acid positions where substitution can occur in the protein. As such, there are 28 amino acid positions where substitution can occur if the protein is 10% nonconserved and has, for example, about 280 amino acids. 2086 protein can also occur deletion of amino acid residues without impairing the immunogenicity of the protein.
[353] In addition, the 2086 protein can be divided into subfamily based on homology of various regions. For example, but not limited to the consensus sequence for two such subgroups, Subfamily A and Subfamily B, are provided below:
[354] 2086 Subfamily A Sequence (SEQ ID NO: 301)
[355]
[356] For reference, "x" is any amino acid.
[357] The region from amino acid position 5 to amino acid position 8 is any 0 to 4 amino acids.
[358] The region from amino acid position 66 to amino acid position 68 is any 0 to 3 amino acids.
[359] The region from amino acid position 5 to amino acid position 8 preferably comprises 0 or 4 amino acids. The region from amino acid position 66 to amino acid position 68 preferably comprises 0 or 3 amino acids.
[360] 2086 Subfamily B (SEQ ID NO: 302)
[361]
[362] For reference, "x" is any amino acid.
[363] The region of amino acid position 8 to amino acid position 12 is any 0-5 amino acid.
[364] The region of amino acid position 8 to amino acid position 12 preferably comprises 0 or 5 amino acids.
[365] In accordance with the practice of the present invention, the 2086 protein subfamily may be further subdivided into populations. For example, in accordance with the practice of the present invention, the following populations are provided: an even sequence of SEQ ID NOs: 2-12; Even sequences in SEQ ID NOs: 14-24; Even sequences in SEQ ID NOs: 26-42; Even sequences in SEQ ID NOs: 50-60; Even sequences in SEQ ID NOs: 62 to 108; The even sequence of SEQ ID NOs: 110-138; The even sequence of SEQ ID NOs: 140 to 156; An even sequence of SEQ ID NOs: 158 to 174; And an even sequence of SEQ ID NOs: 224-252.
[366] Polypeptide sequences of the present invention may be identified with an even reference sequence in SEQ ID NOs: 2 to 252, ie, may include 100% identity or a plurality of amino acid alterations with less than 100% identity (%) relative to the reference sequence. Such alterations include substitution, or insertion, including one or more amino acid deletions, conservative and non-conservative substitutions. The alteration may occur anywhere between the amino- or carboxy-terminal positions of the reference polypeptide sequence or the amino acids of the reference amino acid sequence or between these terminal positions individually interspersed in one or more adjacent groups in the reference amino acid sequence.
[367] Accordingly, the present invention also provides proteins having sequence homology to amino acid sequences contained in the sequence listing (ie, even sequences in SEQ ID NOs: 2 to 252). Depending on the particular sequence, the degree of sequence homology is preferably at least 60% (eg, 60%, 70%, 80%, 90%, 95%, 97%, 99%, 99.9% or more). These homologous proteins include mutants and allelic variants.
[368] In a preferred embodiment of the invention, the 2086 protein or other 2086 polypeptide (eg, immunological moiety and biological equivalent) produces bactericidal antibodies against allogeneic and one or more heterologous strains of meningococcal. In particular, antibodies against 2086 polypeptides passively protect pups from eg intranasal inoculation using meningococcal. In a further preferred embodiment, the 2086 polypeptide exhibits such protection against offspring rats against homologous strains and one or more heterologous strains. The polypeptide may be selected from the above sequence summaries set forth in the even sequence of SEQ ID NOs: 2 to 252, or the polypeptide may be any immunological fragment or biological equivalent of the listed polypeptides. Preferably, the polypeptide is selected from any even sequence of SEQ ID NOs: 2 to 252 in the above sequence summary.
[369] The invention also relates to alleles or other variants of the 2086 polypeptide that are biological equivalents. Suitable biological equivalents include (1) inducing bactericidal antibodies against homologous strains and one or more heterologous Neisseria strains and / or gonococcal strains; (2) react with the surface of the homologous strain and one or more heterologous neisseria and / or gonococcal strains; (3) confer passive protection against surviving inoculum; (4) will exhibit the ability to prevent colonization.
[370] Suitable biological equivalents have at least about 60%, preferably at least about 70%, more preferably at least about 75%, more similarity to one of the 2086 polypeptides described herein (ie, even sequences in SEQ ID NOs: 2 to 252). More preferably about 80% or more, even more preferably about 85%, even more preferably about 90%, even more preferably 95%, even more preferably 98%, even more preferably 99% And equivalents can substantially induce the same immunogenic properties as one of the 2086 proteins of the invention.
[371] Alternatively, the biological equivalents have substantially the same immunogenic properties of one of the 2086 proteins, which are even sequences in SEQ ID NOs: 2 to 252. According to an embodiment of the invention, the biological equivalent has the same immunogenic properties as the even sequence in SEQ ID NOs: 2 to 252.
[372] Biological equivalents are obtained by modifying and altering the proteins of the invention. These modifications and alterations to the protein are obtained by altering the amino acid sequence by insertion, deletion or substitution of one or more amino acids. The amino acid sequence is changed, for example by substitution, to produce a polypeptide having substantially the same or improved properties. Preferred means of introducing alterations include predetermined mutagenesis of the nucleic acid sequence of the polypeptide by site-directed mutagenesis.
[373] Modifications and variations can be made in the structure of the polypeptides of the invention, en. Still obtaining molecules with meningitidis immunogenicity. For example, without limitation, certain amino acids may be substituted (including non-conserved and conserved substitutions) among other amino acids in the sequence without significant loss of immunogenicity. Because this is the interaction capacity and properties of the polypeptides that define the biological functional activity of the polypeptides, many amino acid sequence substitutions can be made in the polypeptide sequence (or, of course, its underlying DNA coding sequence) and nevertheless have similar characteristics. A polypeptide having is obtained. The present invention contemplates any change in the structure of the polypeptides herein as well as the nucleic acid sequences encoding such polypeptides, wherein the polypeptides retain immunogenicity. Those skilled in the art can easily modify the disclosed polypeptides and polynucleotides based on the instructions provided herein.
[374] For example, certain variable regions have been identified where substitutions or deletions are permitted. The 2086 consensus sequence discussed above represents the conserved and non-conserved regions of the 2086 family of proteins in accordance with the practice of the present invention.
[375] In causing such a change, any technique known to those skilled in the art can be used. For example, without limitation, hydrophilicity indicators of amino acids can be considered. The importance of amino acid hydrophilicity indicators in conferring interactive biological functions on polypeptides is generally understood in Kyte et al. 1982. J. Mol. Bio. 157: 105-132.
[376] Substitution of similar amino acids may be made on the basis of hydrophilicity, especially when the biologically functional equivalent polypeptides or peptides produced thereby are used in immunological embodiments. US Pat. No. 4,554,101, incorporated herein by reference, describes that the largest local mean hydrophilicity of a polypeptide governed by the hydrophilicity of its adjacent amino acid correlates with its immunogenicity, ie the biological properties of the polypeptide.
[377] Biological equivalents of polypeptides can also be prepared using site-specific mutagenesis. Site-specific mutagenesis is a technique useful for preparing a second producing polypeptide, or a biologically functional equivalent polypeptide or peptide derived from its sequence through specific mutagenesis of the source DNA. Such changes may be desirable if amino acid substitutions are desired. The technique further provides the ability to introduce one or more nucleotide sequence changes into the DNA, for example, the rapid preparation and testing of sequence modifications embodying one or more of the above considerations. Site-specific mutagenesis is a specific oligonucleotide sequence encoding the DNA sequence of a target mutation, as well as a sufficient number of contiguous primer sequences that provide sufficient size and primer complexity of sequence complexity to form a stable double helix on both sides of the crossing contact. The use of nucleotides allows the production of mutants. Typically, primers having about 5 to 10 residues on all of the contact sides of the altered sequence and about 17 to 25 nucleotides in length are preferred.
[378] Site-specific mutagenesis techniques are generally well known in the art. As will be appreciated, techniques typically use phage vectors that can be present in both single stranded and double stranded forms. Typically, site-directed mutagenesis according to the present disclosure is selected. This is done by first obtaining a single-stranded vector comprising in its sequence a DNA sequence encoding all or part of a meningitidis polypeptide sequence. Oligonucleotide primers having the desired mutation sequence are prepared (eg synthetically). This primer is then annealed to a single-stranded vector and an enzyme such as E. coli. E. coli polymerase I Klenow fragments are used to extend the synthesis of the mutant-owned strands. Thus, a heteroduplex is formed in which one strand originally encodes a non-mutant sequence and the second strand has the desired mutation. This heteroduplex vector is then used to appropriate cells, such as E. coli. E. coli cells are transformed and clones containing the recombinant vector with the mutation are selected. Commercially available kits are available that include all necessary agents except oligonucleotide primers.
[379] The 2086 polypeptide includes any protein or polypeptide having substantially sequence similarity and / or biological equivalence to a 2086 protein having an amino acid sequence from one of the even sequences of SEQ ID NOS: 2 to 252. In addition, the 2086 polypeptides of the invention are not limited to any particular source. Accordingly, the present invention provides for the general detection and isolation of polypeptides from various sources. In addition, the 2086 polypeptide may be prepared recombinantly as is well known in the art based on the instructions provided herein, or may be made by any other synthetic method known in the art.
[380] It is contemplated herein that 2086 polypeptides can be advantageously cleaved into fragments for use in further structural or functional analysis, or preparation of agents such as 2086-related polypeptides and 2086-specific antibodies. It is purified or unpurified yen. Meningitidis polypeptides can be achieved by treatment with peptidase, such as endoproteinase glu-C (Boehringer, Indianapolis, IN). Treatment using CNBr is a peptide fragment that is a natural enzyme. Another method that can be produced from Meningitidis 2086 polypeptide. Recombinant techniques can also be used to produce specific fragments of 2086 protein.
[381] As used herein, a “variant” is a polynucleotide or polypeptide that differs from each of the reference polynucleotides or polypeptides but retains the essential properties. Typical variants of polynucleotides differ in nucleotide sequence from another reference polynucleotide. Changes in the nucleotide sequence of the variant may or may not alter the amino acid sequence of the polypeptide encoded by the reference polynucleotide. Nucleotide changes can result in amino acid substitutions, additions, deletions, fusions, and truncations in the polypeptides encoded by the reference sequences, discussed below. Typical variants of the polypeptide differ in amino acid sequence from another reference polypeptide. In general, the sequences of the reference polypeptide and the variants are almost similar in overall, and are limited so that they differ in the same (ie, biological equivalents) in multiple regions. Variants and reference polypeptides may differ in amino acid sequence by any combination of one or more substitutions, additions, deletions. Substituted or inserted amino acid residues may or may not be encoded by genetic code. Variants of a polynucleotide or polypeptide may be naturally occurring, such as allelic modifications or modifications that are not known to occur naturally. Non-naturally occurring modifications of polynucleotides and polypeptides can be made by mutagenesis techniques or direct synthesis.
[382] "Identity" known in the art is a relationship between two or more polypeptide sequences or two or more polynucleotide sequences determined by comparing sequences. In the art, "identity" also means the degree of sequence involvement between polypeptide or polynucleotide sequences, as the case may be, determined by pairs between such sequence strands. "Identity" and "similarity" can be easily calculated by known methods, including methods described in Computational Molecular Biology, Lesk, AM, ed., Oxford University Press, New York, 1988; Biocomputing: Informatics and Genome Projects , Smith, DW, ed., Academic Press, New York, 1993; Computer Analysis of Sequence Data, Part I, Griffin, AM, and Griffin, HG, eds., Humana Press, New Jersey, 1994; Sequence Analysis in Molecular Biology , von Heinje, G., Academic Press, 1987; and Sequence Analysis Primer, Gribskov, M. and Devereux, J., eds., M Stockton Press, New York, 1991; and Carillo, H., and Lipman, D. , SIAM J. Applied Math., 48: 1073 (1988)). Preferred methods of determining identity are designed to obtain the largest match between the sequences tested. Methods of determining identity and similarity are classified as publicly available computer programs. Preferred computer program methods for determining identity and similarity between two sequences include GCG program packages (Devereux, J., et al 1984), BLASTP, BLASTN, and FASTA (Altschul, SF, et al., 1990). It is not limited to this. The BLASTX program is publicly available from NCBI and other sources (BLAST Manual, Altschul, S., et al., NCBI NLM NIH Bethesda, Md. 20894; Altschul, S., et al., 1990). The well known Smith Waterman algorithm can also be used to determine identity.
[383] By way of example, without limitation, the amino acid sequence of the present invention may be identical (100% identity) to the even sequence of SEQ ID NOS: 2 to 252; Or a plurality of amino acid alterations compared to the reference sequence and less than 100% identity. Such alterations are selected from the group consisting of one or more amino acid deletions, substitutions comprising conservative and non-conservative substitutions, or insertions, said alterations being in the amino- or carboxy-terminal position of the reference polypeptide sequence or in the amino acids of the reference amino acid sequence or It may occur anywhere between these terminal positions individually interspersed in one or more adjacent groups in the reference amino acid sequence. The number of amino acid changes for a given percent identity is multiplied by the total number of amino acids in SEQ ID NOs: 2-252 by the numerical percentage of each percent identity (divided by 100), and then the above of the amino acids in any sequence 2-252 It is determined by subtracting it from the total:
[384]
[385] In the formula,
[386] n _a is the number of amino acid changes,
[387] x _a is the total number of amino acids in SEQ ID NOs: 2 to 252,
[388] y is for example 0.70 for 70%, 0.80 for 80%, 0.85 for 85%, etc.
[389] If x _a and y are not integers, round them to the nearest integer before subtracting it from x _a .
[390] In a preferred embodiment, the polypeptide is selected from mature processed forms of the proteins described in the even sequences of SEQ ID NOS: 2-252, such as 2086 proteins. 2086 proteins or equivalents may be lipidated or non-lipidized.
[391] ORF 2086, along with the native ORF 2086 signal sequence. It is expressible in E. coli. However, it is desirable to find a means of improving protein expression. According to an embodiment of the invention, the leader sequence produces a lipidated form of the protein. For example, the use of signal sequences of nontypable Haemophilus influenzae P4 protein to enhance expression is described below.
[392] Processing of bacterial lipoproteins is initiated by the synthesis of precursor or pre-lipoproteins containing signal sequences, containing consensus lipoprotein processing / modification sites. This pre-lipoprotein passes through the usual Sec system on the inner membrane of gram negative bacteria or on the membrane of gram positive bacteria. When pre-lipoproteins are placed on the membrane by the Sec system, the pre-lipoproteins are cleaved at the consensus site by signal peptidase II, and the exposed N-terminal cysteine residues are glycerylated and acylated (Hayashi et al. Lipoprotein in bacteria.J. Bioenerg.Biomembr. Jun; 22 (3): 451-71; Oudega et al. 1993. Escherichia coli SecB, SecA, and SecY proteins are required for expression and membrane insertion of the bacteriocin release protein , a small lipoprotein.J. Bacteriol.Mar; 175 (5): 1543-7; Sankaran et al. 1995. Modification of bacterial lipoproteins.Method Enzymol. 250: 683-97).
[393] The transport of lipidated proteins from Gram-negative bacteria to the outer membrane is mediated by a unique ABC carrier system with membrane specificity according to the classification signal of lipoprotein at position 2 (Yakushi et al. 2000. A new ABC transporter mediating the detachment of lipid modified proteins from membranes.Nat Cell Biol. Apr; 2 (4): 212-8).
[394] Fusion with bacterial lipoproteins and their signal sequences has been used to display recombinant proteins on the surface of bacteria (US Pat. Nos. 5,583,038 and 6,130,085). The exchange of lipoprotein signal sequences can increase the production of lipoproteins (De et al. 2000. Purification and characterization of Streptococcus pneumoniae palmitoylated pneumococcal surface adhesin A expressed in Escherichia coli.Vaccine.Mar 6; 18 (17): 1811-21 ).
[395] Bacterial lipidation of proteins is known to increase or alter immunological responses to proteins (Erdile et al. 1993. Role of attached lipids in Immunogenicity of Borrelia burgdorferi OspA. Infect. Immun. Jan; 61 (1) ): 81-90; Snapper et al. 1995. Bacterial lipoproteins may substitute forcytokines in the humoral immune response to T cell-independent type II antigens.J. Immunol. Dec 15; 155 (12): 5582-9)). However, bacterial lipoprotein expression can be complicated by the rigor of processing (Pollitt et al. 1986. Effect of amino acid substitutions at the signal peptide cleavage site of the Escherichia coli major outer membrane lipoprotein. J. Biol. Chem. Feb 5 ; 261 (4): 1835-7; Lunn et al. 1987. Effects of prolipoprotein signal peptide mutations on secretion of hybrid prolipo-beta-lactamase in Escherichia coli.J. Biol. Chem. Jun 15; 262 (17): 8318 Klein et al. 1988. Distinctive properties of signal sequences from bacterial lipoproteins.Protein Eng. Apr; 2 (1): 15-20). Bacterial lipoprotein expression is also complicated by other problems, such as toxicity and low expression levels (Gomez et al. 1994. Nucleotide The Bacillus subtilis lipoprotein LplA causes cell lysis when expressed in Escherichia coli. Microbiology. Aug; 140 (Pt 8): 1839-45; Hansson et al. 1995. Expression of truncated and full-length forms of the Lyme disease Borrelia outer surface protein A in Escherichia coli.Protein Expr.Purif. Feb; 6 (1): 15-24; Yakushi et al 1997 Lethality of the covalent linkage between mislocalized major outer membrane lipoprotein and the peptidoglycan of Escherichia coli.J. Bacteriol.May; 179 (9): 2857-62).
[396] Non-type Haemophilus influenzae bacteria express lipoprotein designated P4 (also known as protein "e"). Recombinant forms of the P4 protein can be expressed using native P4 signal sequences. Highly expressed in E. coli (US Pat. No. 5,955, 580). this. The expression level of ORF2086 is increased when the native P4 signal sequence in E. coli is substituted for the native ORF 2086 signal sequence in the expression vector.
[397] This concept of using heterologous P4 signal sequences to increase expression is scalable to other bacterial lipoproteins. In particular, analysis of the bacterial genome leads to the identification of a large number of ORFs, which are as important as possible. Heterologous host cells such as E. coli. Attempts to express each ORF with its natural signal sequence in E. coli cause various inherent problems, including stability, compatibility, and the like in the use of various signal sequences. To minimize these problems, the P4 signal sequence is used to express each desired ORF. As described above, the P4 signal sequence improves the expression of heterologous 2086 ORFs. Expression vectors are constructed by removing the native signal sequence of the desired ORF and ligation of the P4 signal sequence to the ORF. Transforming, transfecting or infecting a suitable host cell with an expression vector then increases the expression of the ORF compared to the expression using the native signal sequence of the ORF.
[398] Non-lipidated forms are produced by leader sequences that have been replaced with regions of the original leader sequence deletion protein or sequences that did not designate a site for fatty acid acylation in the host cell.
[399] Various forms of the 2086 protein of the invention are referred to herein as "2086" proteins unless otherwise noted. Also, “2086 polypeptide” refers to 2086 protein as well as immunogenic portions or biological equivalents thereof, as described above, unless otherwise noted.
[400] Isolated and purified battlefield yen. The apparent molecular weight of Meningitidis 2086 protein is about 28 to 35 kDa as measured on a 10% to 20% gradient SDS polyacrylamide gel (SDS-PAGE). More particularly, the molecular weight of this protein is 26,000 to 30,000 Daltons as measured by mass spectrometry.
[401] Preferably, the 2086 polypeptides and nucleic acids encoding such polypeptides are en. It is used to prevent or ameliorate infections caused by meningitidis and / or other species.
[402] Antibodies
[403] Proteins of the invention, or cells expressing them, comprising the amino acid sequences of SEQ ID NOs: 2 to 252, fragments thereof, and homologues thereof, are also used as immunogens to generate antibody immunospecificity for polypeptides of the invention. The present invention includes antibodies to immunospecific polypeptides, and include N. a. Such antibodies are used to detect the presence of meningitidis to provide passive protection or to measure the dose or concentration of a polypeptide, cell or tissue extract, or biological fluid in a cell.
[404] Antibodies of the invention include polyclonal antibodies, monoclonal antibodies, chimeric antibodies, and anti-idiotype antibodies. Polyclonal antibodies are a heterogeneous population of antibody molecules derived from the serum of an animal immunized with an antigen. Monoclonal antibodies are a substantially homogenous population of antibodies to specific antigens. Monoclonal antibodies can be obtained by methods known in the art, such as by Kohler and Milstein, 1975, Nature 256: 495-497 and US Pat. No. 4,376,110. Such antibodies can be any immunoglobulin class, including IgG, IgM, IgE, IgA, GILD, and any subclass thereof.
[405] Chimeric antibodies are those having variable regions derived from different animal species, such as variable regions derived from murine monoclonal antibodies and human immunoglobulin constant regions. Chimeric antibodies and methods for their production are known in the art (Cabilly et al., 1984, Proc. Natl. Acad. Sci. USA 81: 3273-3277; Morrison et al., 1984, Proc. Natl. Acad. Sci USA 81: 6851-6855; Boulianne et al., 1984, Nature 312: 643-646; Cabilly et al., European Patent Application 125023 (published November 14, 1984); Taniguchi et al., European Patent Application 171496 (published February 19, 1985); Morrison et al., European Patent Application 173494 (published March 5, 1986); Neuberger et al., PCT Application WO 86/01533 (published March 13, 1986); Kudo et al., European Patent Application 184187 (published June 11, 1986); Morrison et al., European Patent Application 173494 (published March 5, 1986); Sahagan et al., 1986, J. Immunol. 137: 1066-1074; Robinson et al., PCT / US86 / 02269 (published May 7, 1987); Liu et al., 1987, Proc. Natl. Acad. Sci. USA 84: 3439-3443; Sun et al., 1987, Proc. Natl. Acad. Sci. USA 84 : 214-218; Better et al., 1988, Science 240: 1041-1043). These references are incorporated herein by reference in their entirety.
[406] Anti-idiotype (anti-Id) antibodies are antibodies that recognize specific determinants generally associated with the antigen-binding site of the antibody. Anti-Id antibodies are prepared by immunizing animals of the same species and genotype (eg, mouse strains) as a source of monoclonal antibodies with monoclonal antibodies from which anti-Ids are made. Immunized animals will generate antibodies against these isotype determinants (anti-Id antibodies) to recognize and respond to the idiotype determinants of the immunized antibody.
[407] Thus, monoclonal antibodies generated against the polypeptides of the invention can be used to induce anti-Id antibodies in a suitable animal. Splenocytes from such immunized mice can be used to generate anti-Id hybridomas that screen for anti-Id monoclonal antibodies. In addition, anti-Id antibodies may be coupled to a carrier such as keyhole limpet hemocyanin (KLH) and used for immunization of additional BALB / c mice. Serum from these mice will contain anti-anti-Id antibodies with binding properties of final mAb specificity for R-PTPase epitopes. Thus, anti-Id antibodies have “idiotopes” such as Streptococcus pyogenes polypeptides that are structurally similarly evaluated to their idiotype epitopes or epitopes.
[408] The term "antibody" is also meant to encompass both intact molecules as well as Fabs capable of binding fragments, such as antigens. Fab fragments may delete Fc fragments of intact antibodies certainly more quickly from circulation and may have less specific tissue binding than intact antibodies (Wahl et al., 1983, J. Nucl. Med. 24: 316- 325). Fabs and other fragments of antibodies useful in the present invention are described according to the method for intact antibody molecules. It will be appreciated that it can be used for the detection and quantification of meningitidis polypeptides.
[409] Antibodies, such as anti-idiotype ("anti-Id") antibodies, of the invention may be used in methods of treating or preventing Neisseria infections in a mammalian host comprising administering an immunologically effective amount of an antibody specific for the polypeptides described above. Can be. Anti-Id antibodies may also be used as “immunogens” to produce so-called anti-anti-Id antibodies in another animal and to induce an immune response. The anti-anti-Id may be epitope identical to the original mAb from which the anti-Id was derived. Thus, the use of antibodies against the idiotype determinant of mAb can identify other clones expressing antibodies of the same specificity.
[410] Antibodies are used in a variety of ways, such as for confirmation of protein expression or to identify where a protein is expressed. Labeled antibodies (eg, fluorescent labels for FACS) can be incubated with intact bacteria and identify the location of the protein, such as by the presence of a label on the bacterial surface.
[411] Antibodies generated against the polypeptides of the invention can be obtained by administering a polypeptide or epitope-containing fragment, homologue, or cell to an animal using conventional protocols. To prepare monoclonal antibodies, any technique that provides antibodies produced in continuous cell line culture is used.
[412] Polynucleotide
[413] With the protein of the invention, the polynucleotide of the invention may comprise a nucleic acid sequence that is identical to, or 100% identical to, any reference sequence of odd sequences in SEQ ID NOs: 1-253, or may comprise a plurality of nucleotides in comparison to a reference sequence. Modifications may include the following. Such alterations are selected from the group consisting of substitutions, or insertions, including one or more nucleotide deletions, transitions, and displacements, wherein the alterations may occur at the 5 'or 3' terminal position of the reference nucleotide sequence or the amino acid of the reference amino acid sequence. It can occur anywhere in between or between these terminal positions individually interspersed in one or more adjacent groups in the reference sequence. The number of nucleotide alterations is determined by multiplying the total number of nucleotides in any odd sequence of SEQ ID NOs: 1-253 by the numerical percentage of each percent identity (divided by 100) and subtracting it from the total number of nucleotides in the sequence.
[414] By way of example, without limitation, an isolated yen. Meningitidis polynucleotides are polynucleotide sequences having at least 70% identity to any of the nucleic acid sequences of SEQ ID NOs: 1-253; Degenerate modifications thereof or fragments thereof, wherein the polynucleotide sequence may comprise no more than n _n nucleic acid alterations over the entire polynucleotide region of the nucleic acid sequence of SEQ ID NOs: 1-253, where _{n n} is the highest number of alterations Calculated by equation 2:
[415]
[416] In the formula,
[417] x _n is the total number of nucleic acids of any of SEQ ID NOs: 1-253,
[418] the value of y is 0.70,
[419] If x _n and y are not integers, round to the nearest integer before subtracting it from x _n .
[420] Of course, y is also 0.80 for 80%, 0.85 for 85%, 0.90 for 90%, 0.95 for 95% and the like. Modifications to a polynucleotide sequence encoding a polypeptide comprising the amino acid sequence of any of SEQ ID NOs: 2 to 252 produce nonsense, missense, or frameshift mutations in this coding sequence and thus are encoded by the polynucleotide according to such alterations. Alter the polypeptide.
[421] Certain embodiments of the present invention relate to polynucleotides encoding the 2086 protein (referred herein as "2086 polynucleotide" or "ORF2086 polynucleotide") and to antibodies generated against the 2086 protein. In a preferred embodiment, an isolated polynucleotide of the present invention comprises a polynucleotide comprising a nucleotide sequence having at least about 95% identity to a nucleotide sequence selected from one of the odd sequences in SEQ ID NOs: 1-253, or a degenerate modification thereof, or It is a fragment. As defined herein, a “degenerate modification” differs from the nucleotide sequence (and fragment thereof) shown in the odd sequence of SEQ ID NOs: 1-253 because of the degeneracy of the genetic code, but the nucleotide sequence shown in the odd sequence of SEQ ID NOs: 1-253. It is defined as a polynucleotide encoding the same 2086 protein (ie, the even sequence of SEQ ID NOS: 2 to 252) as encoded by.
[422] In other embodiments, the polynucleotide is complementary to a nucleotide sequence selected from one of the odd sequences of SEQ ID NOs: 1-253, a degenerate modification thereof, or a fragment thereof. In still other embodiments, the polynucleotide is selected from the group consisting of DNA, chromosomal DNA, cDNA and RNA, and may comprise heterologous nucleotides. In another embodiment, the isolated polynucleotide hybridizes under highly stringent hybridization conditions to a nucleotide sequence selected from one of SEQ ID NOs: 1-253, its complement, a degenerate modification thereof, or a fragment thereof. In still other embodiments, the polynucleotides hybridize under moderate stringent hybridization conditions.
[423] It will be appreciated that 2086 polynucleotides may be obtained from natural, synthetic or semi-synthetic sources; In addition, the nucleotide sequence may be a naturally occurring sequence or may be related by mutations including single or multiple base substitutions, deletions, insertions, and inversions to such naturally occurring sequences, wherein the nucleic acid molecules comprising such sequences It always provides that it can be expressed as a 2086 immunogenic polypeptide as described above. Nucleic acid molecules can be RNA, DNA, single- or double-stranded, linear or covalently closed rings. Nucleotide sequences have expression control sequences located adjacent to them, which can usually be derived from heterologous sources. In general, recombinant expression of a nucleic acid sequence of the invention will use a stop codon sequence, such as TAA, at the end of the nucleic acid sequence.
[424] The invention also encompasses polynucleotides that can hybridize to the polynucleotides described herein under reduced stringent conditions, more preferably stringent conditions, and most preferably highly stringent conditions. Examples of stringent conditions are shown in the following stringent conditions table I: highly stringent conditions are, for example, stringent by conditions A to F or higher; Stringent conditions are, for example, stringent by conditions G to L or higher; Reduced stringent conditions are, for example, stringent conditions by conditions M to R or higher.
[425]
[426] bp ^I : Hybrid length is the expected length for the hybridized region (s) of the hybridizing polynucleotide. When polynucleotides hybridize to target polynucleotides of unknown sequence, the hybrid lengths add up to the length of the hybridized polynucleotides. When polynucleotides of known sequence hybridize, the hybrid length can be measured by aligning the sequences of the polynucleotides and identifying regions or regions of optimal sequence complementarity.
[427] Buffer ^H : SSPE (1 x SSPE is 0.15 M NaCl, 10 mM NaH ₂ PO ₄ , and 1.25 mM EDTA, pH 7.4) is the SSC during hybridization (1 x SSC is 0.15 M NaCl and 15 mM sodium citrate) and Can be replaced for wash buffer; Washing is performed for 15 minutes after completion of hybridization.
[428] T _B to T _R : The hybridization temperature for hybrids with lengths expected to be less than 50 base pairs should be 5-10EC below the hybrid's melting temperature (T _m ), where T _m is determined according to the following equation. For hybrids less than 18 base pairs in length, T _m (EC) = 2 (number of A + T bases) + 4 (number of G + C bases). For hybrids of 18 to 49 base pairs in length, T _m (EC) = 81.5 + 16.6 (log ₁₀ [Na ⁺ ]) + 0.41 (% G + C)-(600 / N), where N is the number of bases of the hybrid And [Na ⁺ ] is the concentration of sodium ions in the hybridization buffer ([Na +] = 0.165 M for 1 x SSC).
[429] Stringent additional examples of polynucleotide hybridization are described in Sambrook, J., EF Fritsch, and T. Maniatis, 1989, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, chapters 9 and 11, and Current Protocols in Molecular Biology, 1995, FM Ausubel et al., Eds., John Wiley & Sons, Inc., sections 2.10 and 6.3-6.4, which are incorporated herein by reference.
[430] The present invention also provides polynucleotides that are completely complementary to these polynucleotides, and also provide antisense sequences. Antisense sequences of the invention (also referred to as antisense oligonucleotides) include both internally generated or externally administered sequences that block the expression of a polynucleotide encoding a polypeptide of the invention. Antisense sequences of the invention include, for example, about 15 to 20 base pairs. Antisense sequences can be designed to inhibit transcription, for example, by blocking a promoter binding to an upstream untranslated sequence or by blocking the translation of a transcript encoding a polypeptide of the invention by blocking ribosomes from binding.
[431] Polynucleotides of the invention are prepared in a number of ways (eg, by chemical synthesis, from DNA libraries, from their own organisms), and in various forms (eg, single-stranded, double-stranded, vectors, probes, primers) Can be obtained. The term "polynucleotide" includes DNA and RNA, as well as homologues thereof, such as modified backbones.
[432] According to a further implementation of the invention, a polynucleotide of the invention comprises a DNA library, such as a cDNA library.
[433] Fusion protein
[434] The invention also relates to fusion proteins. A "fusion protein" refers to a protein encoded by two (often non-associated) fusion genes or fragments thereof. For example, a fusion protein includes various portions of the constant region of an immunoglobulin molecule along with another immunogenic protein or portion thereof. In many cases, the use of an immunoglobulin Fc region as part of a fusion protein is advantageous for use, for example, in the treatment and diagnosis resulting in improved pharmacokinetic properties (see eg EP 0 232 262A1). On the other hand, for some uses it will be desirable to be able to delete the Fc moiety after the fusion protein is expressed, detected and purified. The 2086 polynucleotides of the invention are used for recombinant production of polypeptides of the invention, and the polynucleotides are themselves encoded by coding sequences for mature polypeptides, or other coding sequences, such as leader or secretory sequences, pre-, or pro- or pripes. Coding sequence for the mature polypeptide in the reading frame having a low-protein sequence, or other fusion peptide moiety. For example, marker sequences that facilitate purification of 2086 polypeptides or fusion polypeptides can be encoded (see Gentz et al., 1989, which is incorporated herein by reference in its entirety). Accordingly, the preparation of polynucleotides encoding fusion polypeptides that allows His-tag purification of expression products in the practice of the present invention is contemplated. Polynucleotides may also contain non-coding 5 'and 3' sequences such as translation, non-translation sequences, splicing and polyadenylation signals. Such fusion polypeptides may be produced by transformed / transfected or infected porcine cells with the recombinant DNA cloning vehicle described below, and then isolated from the host cell to provide a fusion polypeptide that is substantially free of other host cell proteins. .
[435] Immunogenic Compositions
[436] One aspect of the invention provides an immunogenic composition comprising one or more 2086 proteins or nucleic acids encoding said proteins. The above (1) induces sterile antibodies against a plurality of strains; (2) react with the surface of multiple strains; (3) confer passive protection against surviving inoculum; (4) Has the ability to prevent colonization.
[437] Formulations of such immunogenic compositions are well known to those skilled in the art. The immunogenic composition of the invention preferably comprises a pharmaceutically acceptable carrier. Suitable pharmaceutically acceptable carriers and / or diluents include any and all conventional solvents, dispersion media, fillers, solid carriers, liquid solutions, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like. Suitable pharmaceutically acceptable carriers include, for example, one of water, saline, phosphate buffered saline, dextrose, glycerol, ethanol and the like, as well as combinations thereof. Pharmaceutically acceptable carriers may further comprise minor amounts of auxiliary substances, such as wetting or emulsifying agents, preservatives or buffers, which enhance the half-life or potency of the antibody. The preparation and use of pharmaceutically acceptable carriers are well known in the art. Except insofar as it is incompatible with the active ingredient as any conventional media or agent, its use in the immunogenic compositions of the present invention is contemplated.
[438] Such immunogenic compositions can be administered parenterally, such as by injection, subcutaneous or intramuscular, as well as orally or intranasally. Intramuscular immunization methods are described by Wolf et al. And Sedegah et al. Other modes of administration include, but are not limited to, oral formulations, pulmonary formulations, suppositories, and transdermal application. Oral formulations include, for example and without limitation, such commonly used excipients such as pharmaceutical grade mannitol, lactose, starch, magnesium stearate, sodium saccharin, cellulose, magnesium carbonate and the like.
[439] Immunogenic compositions of the invention include aluminum hydroxide; Aluminum phosphate; STIMULON® QS-21 (Aquila Biopharmaceuticals, Inc .; Framingham, MA); MPL® (3-O-Deacylated Monophosphoryl Lipid A; Corixa; Hamilton, MT), 529 (Amino Alkyl Glucosamine Phosphate Compound; Corica; Hamilton, MT), IL-12 (Genetics Genetics Institute, Cambridge, MA); GM-CSF (Immunex Corp .; Seattle, Washington); N-acetyl-muramil-L-teronyl-D-isoglutamine (thr-MDP); N-acetyl-nor-muramil-L-alanyl-D-isoglutamine (CGP 11637, referred to as nor-MDP); N-Acetyl-murayl-L-alanyl-D-isoglutaminyl-L-alanine-2- (1'-2'-dipalmitoyl-sn-glycero-3-hydroxyphosphoryloxy-ethyl Amines) (CGP 19835A, referred to as MTP-PE); And one or more adjuvants, including but not limited to cholera toxin. Other that may be used are cholera toxins, including the A subunit of cholera toxins, and / or N. Conjugates or genetically engineered fusions of meningitidis polypeptides with cholera toxin, or their B subunits ("CTBs"), fungal polysaccharides including schizophyllan, procholeragenoids, muramyl dipeptides, muramyl dipeptides ( "MDP") derivatives, phorbol esters, 2. E. coli is a heat labile toxin, block polymer or saponin.
[440] In certain preferred embodiments, the proteins of the invention are used in immunogenic compositions for oral administration comprising mucosal adjuvants and in human hosts. Used to treat or prevent meningitidis infections. The mucosal adjuvant may be a cholera toxin; Preferably, mucosal adjuvants other than cholera toxin that can be used according to the present invention include non-toxic derivatives of cholera holotoxin, wherein the A subunit is mutated and chemically modified cholera toxin, or cholera toxin amino acid It is a related protein produced by modification of the sequence. For specific cholera toxins that may be particularly useful for preparing the immunogenic compositions of the present invention, refer to the mutant cholera holotoxin E29H disclosed in WO 00/18434, which is incorporated by reference in its entirety. These may be added to or conjugated to the polypeptides of the invention. The same technique can be applied to mucosal adjuvants or other molecules with delivery properties such as Escherichia coli heat labile toxin (LT). Mucosal adjuvants or other compounds with delivery activity, such as bile; Polyvalent cations such as DEAE-dextran and polyornithine; Detergents such as sodium dodecyl benzene sulfate; Lipid-conjugated materials; Antibiotics such as streptomycin; Vitamin A; And other compounds that alter the structure or functional integrity of the mucosal surface. Other mucosal active compounds include derivatives of microbial structures, such as MDP; Acridine and cimetidine. STIMULON® QS-21, MPL, and IL-12 as described above can also be used.
[441] Immunogenic compositions of the invention are delivered in the form of ISCOMS (immune stimulating complexes), CTB containing ISCOMS, liposomes, or encapsulated with compounds such as acrylates or poly (DL-lactide-co-glycosides), Microspheres can be formed. Proteins of the invention can also be incorporated into oily emulsions.
[442] Multiple antigens
[443] Immunogenic agents, including proteins, polynucleotides, and equivalents of the invention may be administered as the sole active immunogen in an immunogenic composition, or alternatively, the composition may comprise other Neisseria species immunogenic polypeptides, or one or more other microbial pathogens ( Other active immunogens, including but not limited to immunologically active proteins or capsular polysaccharides of viruses, prions, bacteria, or fungi). The composition may comprise one or more target proteins, fragments or pharmaceutical compounds as desired for the selected indication. In the same way, compositions of the invention using one or more nucleic acids in an immunogenic composition may also comprise nucleic acids encoding the same various proteins as described above.
[444] Any multi-antigen or multivalent immunogenic composition is contemplated by the present invention. For example, a composition of the present invention may be used in combination with two or more 2086 proteins, a combination of 2086 protein and one or more Por A proteins, with 2086 protein and meningococcal serogroups A, C, Y, and W135 polysaccharides and / or polysaccharide conjugates. Combinations, combinations of 2086 protein with meningococcal and pneumococcus combinations, or combinations of any of the foregoing, in a form suitable for mucosal delivery. One skilled in the art can readily formulate such multi-antigen or multivalent immunogenic compositions.
[445] The present invention also contemplates multi-immunization therapies in which any composition useful for the pathogen can be formulated therein or combined with the composition of the invention. For example, but not limited to, the immunogenic composition and S. a. Other immunological compositions for immunization against pneumoniae can be administered as part of a multi-immunization therapy. Those skilled in the art can readily select immunogenic compositions for use with the immunogenic compositions of the present invention for the purpose of developing and practicing multi-immunization therapies.
[446] Certain embodiments of the present invention are directed to S. a. One or more polypeptides of the invention, or nucleic acids encoding them, in a composition for the prevention or alleviation of pneumoniae infection or as part of a therapy. 2086 polypeptide or 2086 polynucleotide. It can be combined with any immunogenic composition for use against pneumoniae infection. It is also possible to combine 2086 polypeptide or 2086 polynucleotide with any other protein or polysaccharide based meningococcal vaccine.
[447] 2086 polypeptides, fragments and equivalents can be used as part of a conjugate immunogenic composition, wherein one or more proteins or polypeptides are used to produce a composition having immunogenic properties for some serotypes and / or for some diseases. It may be conjugated to a carrier. Alternatively, one of the 2086 polypeptides can be used as a carrier protein for other immunogenic polypeptides.
[448] The invention also relates to a method of inducing an immune response in a mammal comprising providing the mammal with an immunogenic composition of the invention. The immunogenic composition is antigenic in the treated animal or human so that the immunologically effective amount of the polypeptide (s) contained in such composition is contained. A composition that generates a desired immune response against meningitidis infection. Preferred embodiments include administering an immunologically effective amount of the composition to a human. It relates to a method of treatment including alleviation or prevention of meningitidis infection.
[449] As used herein, the phrase “immunologically effective amount” is administered to a mammalian host (preferably human) as a single dose or as part of a series of doses such that the immune system of the individual to be treated reduces at least the clinical impact of bacterial infection. It is meant an amount sufficient to generate a reaction to make. This can range from minimal reduction in bacterial burden to infection prevention. Ideally, the treated subject will not show more severe clinical signs of bacterial infection. Dosage may vary depending on the particular condition of the individual. Such amounts can be determined by routine practice or by methods known to those skilled in the art otherwise.
[450] Another specific aspect of the invention relates to the use of a vector or plasmid expressing a protein of the invention or an immunogenic portion thereof as an immunogenic composition. Accordingly, a further aspect of the invention provides a method of inducing an immune response in a mammal comprising providing the mammal with a vector or plasmid expressing one or more isolated 2086 polypeptides. Proteins of the invention can be delivered to mammals using live vectors, in particular using live recombinant bacteria, viruses or polypeptides or other live agents containing the genetic material necessary for the expression of the immunogenic portion as foreign polypeptides.
[451] According to a further embodiment of the present invention, the method comprises detecting the presence of an immune complex or tissue sample from the mammal, wherein the mammal or tissue sample is any one of the even numbers SEQ ID NOs: 2 to 252. Bacterial meningitis in a mammal, wherein the antibody is coupled to an antibody composition comprising an antibody that immunospecifically binds one or more polypeptides comprising an amino acid sequence of a protein, wherein the mammalian or tissue sample is contacted with the antibody composition under conditions suitable for the formation of an immune complex. To provide a diagnostic method.
[452] Viral and non-viral vectors
[453] Particularly preferred vectors for in vitro and in vivo cell analysis are viral vectors such as lentiviruses, retroviruses, herpes virus, adenovirus, adeno-associated virus, vaccinia virus, baculovirus, and other recombinant viruses with desirable bacterial flavours. to be. Thus, nucleic acids encoding 2086 proteins or immunogenic fragments thereof can be introduced in vivo, in vitro, or in vitro using viral vectors or through direct introduction of DNA. Expression in targeted tissues can be performed, for example, by targeting the transgenic vector to specific cells with a viral vector or receptor ligand, using a tissue-specific promoter, or both. Targeted gene delivery is described in PCT Publication No. WO 95/28494, which is incorporated by reference in its entirety.
[454] Viral vectors commonly used in in vivo or in vitro targeting and therapy procedures are DNA based vectors and retroviral vectors. Methods of constructing and using viral vectors are known in the art (see, eg, Miller and Rosman, BioTechniques, 1992, 7: 980-990). Preferably, viral vectors are replication-deficient, ie they cannot autonomously replicate in target cells. Preferably, the replication deficient virus is a minimal virus, ie it retains only the sequence of the genome necessary to encapsulate the genome to produce viral particles.
[455] DNA viral vectors include, but are not limited to, attenuated or deficient DNA viruses such as herpes simplex virus (HSV), papillomavirus, Epstein Barr virus (EBV), adenovirus, adeno-associated virus (AAV), and the like. Preferred are those that lack a viral gene completely or almost completely. The deficient virus is not infectious after introduction into the cell. The use of a deficient viral vector allows administration to cells at specific localized sites regardless of whether the vector can infect other cells. Thus, specific tissues can be specifically targeted. Examples of unique vectors include a deficient herpes virus 1 (HSV1) vector (Kaplitt et al., Molec. Cell. Neurosci., 1991, 2: 320-330), a deficient herpes virus vector lacking the glycoprotein L gene, or other deficiency. Herpes virus vectors (PCT Publications WO 94/21807 and WO 92/05263); Attenuated adenovirus vectors, such as, for example, Stratford-Perricaudet et al., J. Clin. Invest., 1992, 90: 626-630; La Salle et al., Science, 1993, 259: 988-990 The vector described in; And deficient adeno-associated viral vectors (Samulski et al., J. Virol., 1987, 61: 3096-3101; Samulski et al., J. Virol., 1989, 63: 3822-3828; Lebkowski et al., Mol Cell. Biol., 1988, 8: 3988-3996, which is incorporated herein by reference in its entirety.
[456] Avigen, Inc .; Alameda, CA; AAV vector), Cell Genesys; Foster City, CA; retrovirus, adenovirus, AAV vector, and lentiviral vector), clonetech ( Clontech; retrovirus and baculovirus vectors), Genovo, Inc. (Genovo, Inc .; Sharon Hill, PA; adenovirus and AAV vectors), Genvec (adenovirus vectors), IntroGene; Leiden, Netherlands; adenovirus vectors), molecular medicine (Molecular Medicine; retroviruses, adenoviruses, AAV, and herpes virus vectors), norgens (adenovirus vectors), Oxford BioMedica (Oxford BioMedica; Oxford, United Kingdom; lentiviral vectors), and Transgene; Strasbourg, France; adenovirus, vaccinia, retrovirus, and lentiviral vectors) Which is a company producing viral vectors commercially, it is fully incorporated herein by reference.
[457] Adenovirus vector. Adenoviruses are eukaryotic DNA viruses that can be modified to efficiently deliver nucleic acids of the invention to a variety of cell types. There are various serotypes of adenoviruses. Of these serotypes, type 2 or 5 human adenoviruses (Ad 2 or Ad 5) or adenoviruses of animal origin (see PCT Publication No. WO 94/26914) are preferred within the scope of the present invention. Such adenoviruses of animal origin that can be used within the scope of the present invention include dogs, cattle, mice (e.g. Mavl, Beard et al., Virology, 1990, 75-81), sheep, pigs, birds and apes (e.g. SAV) adenoviruses of origin. Preferably, the adenovirus of animal origin is canine adenovirus, more preferably CAV2 adenovirus (eg Manhattan or A26 / 61 strain ATCC VR-800). Various replication deficient adenovirus and minimal adenovirus vectors are described in PCT Publications WO 94/26914, WO 95/02697, WO 94/28938, WO 94/28152, WO 94/12649, WO 95/02697, WO 96/22378). Replication deficient recombinant adenoviruses according to the present invention can be prepared by any technique known to those skilled in the art (Levrero et al., Gene, 1991, 101: 195; European Publication EP 185 573; Graham, EMBO J., 1984, 3: 2917). Graham et al., J. Gen. Virol., 1977, 36:59). Recombinant adenoviruses are recovered and purified using standard molecular biological techniques well known to those skilled in the art.
[458] Adeno-associated virus. Adeno-associated viruses (AAV) are relatively small DNA viruses that can integrate into the genome of cells infected by the virus in a stable and site-specific manner. They can infect a wide range of cells without inducing any effect on cell growth, morphology or differentiation and they do not appear to be involved in human pathology. The AAV genome has been cloned, sequenced and characterized. The use of vectors derived from AAV to deliver genes in vitro and in vivo is described in PCT Publications WO 91/18088 and WO 93/09239; US Pat. Nos. 4,797,368 and 5,139,941; Europe Publication EP 488 528). Replication deficient recombinant AAV according to the present invention comprises a plasmid containing a nucleic acid sequence of interest flanked by two AAV reverse terminal repeat (ITR) regions, and an AAV capsidation gene (rep and cap gene) carrying plasmid, which is characterized by human helper virus ( For example, it can be prepared by cotransfecting a cell line infected with adenovirus). The prepared AAV recombinants are then purified by standard techniques.
[459] Retrovirus Vectors. In another embodiment of the invention, nucleic acids are incorporated herein by reference in their entirety (see, eg, US Pat. No. 5,399,346; Mann et al., Cell, 1983, 33: 153; US Pat. No. 4,650,764) And US Pat. Nos. 4,980,289; Markowitz et al., J. Virol., 1988, 62: 1120; US Pat. No. 5,124,263; European Publications EP 453 242 and EP 178 220; Bernstein et al., Genet. Eng , 1985, 7: 235; McCormick, BioTechnology, 1985, 3: 689; PCT Publication WO 95/07358; and Kuo et al., Blood, 1993, 82: 845). can do. Retroviruses incorporate viruses that infect dividing cells. The retroviral genome comprises two LTRs, capsidizing sequences and three coding regions (gag, pol and env). In recombinant retroviral vectors, the gag, pol and env genes are generally deleted, in whole or in part, and substituted with heterologous nucleic acid sequences of interest. These vectors include different types of retroviruses such as HIV, MoMuLV ("Moloney leukaemia virus"), MSV ("murine Moloney sarcoma virus"), HaSV ("Harvey Sarcoma virus "); SNV ("spleen necrosis virus"); It can be constructed from RSV (“Rous sarcoma virus”) and Friend virus. Suitable packaging cell lines are described in the prior art, in particular cell line PA317 (US Pat. No. 4,861,719); PsiCRIP cell line (PCT Publication No. WO 90/02806) and GP + envAm-12 cell line (PCT Publication WO 89/07150). In addition, recombinant retroviral vectors may contain modifications within a wide range of capsidation sequences that may include part of the gag gene as well as LTR to inhibit transcriptional activity (Bender et al., J. Virol., 1987, 61: 1639). Recombinant retroviral vectors are purified by standard techniques known to those skilled in the art.
[460] Retroviral vectors can be constructed to act as infectious particles or to undergo a single cycle of infection. In the former case, the virus is constructed to retain all of its genes and to express heterologous genes except to cause oncogenic transformation properties. Non-infectious viral vectors disrupt viral packaging signals, but are constructed to retain the structural genes needed to package co-introduced viruses engineered to contain heterologous genes and packaging signals. As such, the virus particles produced are unable to produce additional viruses.
[461] Retroviral vectors can also be introduced by DNA viruses, which enable one cycle of retroviral replication and amplify infection efficiency (see PCT Publications WO 95/22617, WO 95/26411). 96/39036 and WO 97/19182).
[462] Lentiviral vector. In another embodiment of the invention, lentiviral vectors can be used as agents for direct delivery and sustained expression of transgenes in several tissue types including brain, retina, muscle, liver and blood. The vector can efficiently transduce dividing and non-dividing cells in the tissue and perform long term expression of the gene of interest. For a review, see Naldini, Curr. Opin. Biotechnol., 1998, 9: 457-63; Zufferey, et al., J. Virol., 1998, 72: 9873-80. Lentivirus packaging cell lines are available and are generally known in the art. They facilitate the production of high-titer lentiviral vectors for gene therapy. One example is a tetracycline-derived VSV-G pseudotype lentiviral packaging cell line capable of producing viral particles at titers of at least 106 IU / mL for at least 3 to 4 days (Kafri, et al., J. Virol., 1999, 73: 576-584). Vectors prepared by inducible cell lines can optionally be enriched for efficient transduction of non-dividing cells in vitro and in vivo.
[463] Non-viral vector. In another embodiment of the invention, the vector can be introduced in vivo by lipofection, naked DNA, or using other transfection promoters (peptides, polymers, etc.). Synthetic cationic lipids can be used to prepare liposomes for in vivo transfection of genes encoding markers (Felgner, et. Al., Proc. Natl. Acad. Sci. USA, 1987, 84: 7413-). 7417; Felgner and Ringold, Science, 1989, 337: 387-388; Mackey, et al., Proc. Natl. Acad. Sci. USA, 1988, 85: 8027-8031; Ulmer et al., Science, 1993, 259 1745-1748). Lipid compounds and compositions useful for the transformation of nucleic acids are described in PCT Publications WO 95/18863 and WO 96/17823, and US Pat. No. 5,459,127. Lipids can be chemically coupled to other molecules for targeting purposes (Mackey, et al., Supra). Targeted peptides such as hormones or neurotransmitters, and proteins such as antibodies, or non-peptide molecules can be chemically coupled to liposomes.
[464] Cationic oligopeptides (cf. PCT Patent Publication No. WO 95/21931), peptides derived from DNA binding proteins (cf. PCT Patent Publication No. WO 96/25508), or cationic polymers (cf. PCT Patent) Other molecules such as WO 95/21931) are also useful for promoting transfection of nucleic acids in vivo.
[465] It is also possible to introduce the vector in vivo as a naked DNA plasmid. DNA vectors that are intended for vaccine purposes or for gene therapy are known in the art, such as electroporation, microinjection, cell fusion, DEAE dextran, calcium phosphate precipitation, use of gene guns, or use of DNA vector transporters. (See, eg, Wu et al., J. Biol. Chem., 1992, 267: 963-967; Wu and Wu, J. Biol. Chem., 1988, 263: 14621-14624; Canadian Patent Application No. 2,012,311; Williams et al., Proc. Natl. Acad. Sci. USA, 1991, 88: 2726-2730). Receptor-mediated DNA delivery methods can also be used (Curiel et al., Hum. Gene Ther., 1992, 3: 147-154; Wu and Wu, J. Biol. Chem., 1987, 262: 4429-4432). . US Pat. Nos. 5,580,859 and 5,589,466 disclose the delivery of exogenous DNA sequences in the absence of infection promoters in mammals. Recently, a relatively low voltage, high efficiency in vivo DNA delivery technique called electrotransmission has been described (Mir et al., CP Acad. Sci., 1988, 321: 893; PCT Publication WO 99/01157; WO 99). / 01158; WO 99/01175). Thus, a further embodiment of the present invention comprises administering to a human an amount of a DNA molecule encoding a 2086 polypeptide of the invention, optionally with a transfection promoter, wherein said polypeptide retains immunogenicity when expressed, Neisseria spp pathogens such as N. when incorporated into an immunogenic composition and administered to a human. A method of inducing an immune response in humans, which provides protection without inducing aggravated disease upon subsequent infection of the human with meningitidis. Transfection promoters are known in the art and include bupivacaine and other local anesthetics (see, eg, US Pat. No. 5,739,118) and cationic polyamines (published in International Patent Application WO 96/10038). Is incorporated herein by reference in its entirety.
[466] The present invention also relates to antibodies (which may be monoclonal or polyclonal antibodies) specific for the 2086 polypeptide described above. Such antibodies can be prepared by methods known to those skilled in the art.
[467] Bacterial Expression Systems and Plasmids
[468] The invention also provides a recombinant DNA molecule (eg, vector or plasmid) comprising an expression control sequence having a promoter sequence and an initiation sequence, and a nucleotide sequence encoding the polypeptide of the invention (located 3 'to the promoter and initiation sequence) ). In another aspect, the invention is capable of expressing a 2086 polypeptide comprising an expression control sequence having a promoter sequence and an initiation sequence, and a nucleotide sequence encoding the 2086 polypeptide (located 3 'to the promoter and initiation sequence). Provide a recombinant DNA cloning vehicle. In a further aspect, a host cell containing the recombinant DNA cloning vehicle and / or recombinant DNA molecules described above is provided. Combinations of suitable expression control sequences and host cell / cloning vehicles are known in the art and are described, eg, in Sambrook et al (1989).
[469] If a recombinant cloning vehicle and / or host cell expressing a preferred polypeptide of the invention is formed by transforming, transfecting or infecting a plasmid containing the corresponding 2086 polynucleotide with the cloning vehicle or host cell, the cloning vehicle or host The cells are cultured under conditions where the polypeptide is expressed. The polypeptide is then isolated with substantially contaminating host cell components removed by methods known to those skilled in the art.
[470] The following examples are included to illustrate preferred embodiments of the present invention. It will be appreciated by those skilled in the art that the described embodiments according to the representative techniques found by the inventors are useful in the practice of the present invention, and thus can be regarded as constituting a preferred manner for the practice of the present invention. However, those skilled in the art will recognize that various specific embodiments disclosed in light of the present disclosure may vary, and that such changes may yield the same or similar results without departing from the spirit and scope of the present invention.
[471] Example 1
[472] Identification of Neisseria Membrane Protein Extracts That Induce Bactericidal Antibodies Against Heterologous Strains
[473] As shown in Table II below, LOS-depleted outer membrane protein preparations were found to induce bactericidal antibodies. This antibody is often directed directly against PorA of each strain. LOS-depleted outer membrane protein preparations from serogroup B meningococcal strain 8529 (B: 15: P1.7b, 3) were unique in this method because they unexpectedly induced bactericidal antibodies against several heterologous strains.
[474]
[475] In order to easily isolate and characterize antigens that induce heterologous bactericidal antibodies, the inventors investigated detergents that extract antigens optimally.
[476] Strains and Culture Conditions:
[477] Yen in a frozen vial. Meningitidis strain 8529 was streaked on GC plates (meningococcal strain 8529 was obtained from RIVM, (Bilthoven, The Netherlands)). Plates were incubated at 36 ° C./5% CO ₂ for 7.5 hours. Several colonies were inoculated into flasks containing 50 ml of controlled Franz medium supplemented with GC. The flask was incubated at 36 ° C. in an air shaker and stirred at 200 RPM for 4.5 hours. 5 mL of this was inoculated into a Fernbach flask containing 450 ml of controlled Franz medium supplemented with GC. The flask was incubated at 36 ° C. in an air shaker and stirred at 100 RPM for 11 hours. All 450 mL were inoculated into a 10 L fermentor containing 8.5 L of controlled Franz medium supplemented with GC.
[478] Composition of controlled Franz medium:
[479] Glutamic Acid 1.3 g / L
[480] Cysteine 0.02 g / L
[481] Sodium Phosphate (Dibasic, Heptahydrate) 10 g / L
[482] Potassium chloride 0.09 g / L
[483] Sodium chloride 6 g / L
[484] Ammonium Chloride 1.25 g / L
[485] Dialysis Yeast Extract (YE) 40 ml
[486] (25% YE solution; dialyzed overnight for 5 volumes of dH ₂ O, autoclaved)
[487] GC supplement 100 X, sterilized by filter
[488] Dextrose 400 g / L
[489] Glutamic Acid 10 g / L
[490] Cocarboxylase 0.02 g / L
[491] Ferric Nitrate 0.5 g / L
[492] The following parameters were adjusted during the fermentation process: temperature = 36 ° C; pH = 7.4; Dissolved oxygen = 20%. A few drops of P-2000 antifoam were added to control the foaming phenomenon. The culture was incubated to normal stage. Cells were harvested by centrifugation when the OD ₆₅₀ value was 5.25. Typically, a total of 100 to 300 mg of wet cell paste was harvested from ˜8.5 L of culture.
[493] Partial Purification of Outer Membrane Protein Fraction from Meningococcal Inducing Heterologous Bacterial Antibodies
[494] 100 g of wet weight cells were suspended in 10 mM HEPES-NaOH (pH 7.4), 1 mM Na ₂ EDTA to a volume 5 times the wet weight, and through a chamber-mounted 110 Y microfluidizer. The cells were lysed by passing at 18,000 psi. Cell lysis was washed and the cell envelope was isolated by centrifugation at 10 ° C. for 1 hour at 300,000 × g. The cell envelope was suspended in a homogenizer and washed twice with the same buffer, followed by centrifugation as above. The cell envelope was then extracted with 320 mL of 1 wt / vol% Triton X-100 in 10 mM HEPES-NaOH (pH 7.4), 1 mM MgCl ₂ . As shown in Table III below, the results obtained by sequentially sequencing with different washes using Triton X-100 and Zwittergent 3-14 resulted in immunization of mice to extract which Triton extract would be of optimal interest. To determine whether the This Triton X-100 extract (inducing a bactericidal antibody that reacts against four of the five strains listed in Table III) was subjected to BioRad Rotophor unit by preparative isoelectric focusing (IEF). Fraction from The concentration of the amphoteric electrolyte was 1% pH 3-10 mixed with 1% pH 4-6. As shown in Table III, several fractions have been found that induce heterogeneous bactericidal responses. Fractions obtained from the IEF (pH adjusted to 5.5 to 7.8) elicited heterologous responses for most strains as determined by bactericidal analysis. The collected IEF fractions were concentrated and the positive electrolyte was removed by ethanol precipitation. Some of the proteins having a pH value in the range of about 5.5-7.9 were adsorbed on an anion exchange column and further purified by comparing the bactericidal activity obtained after immunizing mice with adsorbed and non-adsorbed proteins. Again, as shown in Table II, a number of proteins were adsorbed to the anion exchange resin, whereas the nonadsorbed proteins in the column induced more heterologous bactericidal antibodies.
[495]
[496] As shown in FIG. 1A, two major proteins were present in the nonadsorbed fractions determined by SDS-PAGE. Two types of assays were performed to identify this protein. One assay is a method for isolation of peptides after limited proteolysis (see FIGS. 1A and 1B) to perform direct protein sequencing. Other assays were performed after SDS-PAGE, followed by gel cleavage, proteolysis and NC-MS / MS (Liquid Chromatography tandem Mass Spectrometry) (see Figure 3) to mass for the components of the formulation of interest. A method of obtaining spectroscopic information (see peptide mapping and sequencing methods described later in this paragraph).
[497] yen. Meningitidis Sanger genomic sequences were analyzed using the methods and algorithms described in Zagursky and Russell, 2001, BioTechniques, 31: 636-659. The analysis identified more than 12,000 possible open reading frames (ORFs). Both the direct sequence data and the mass spectroscopic data described above indicate that the main components of the non-adsorbed fraction are the products of some ORFs present in the analysis of the Sanger database. Three potent proteins identified by this method corresponded to ORF 4431, 5163 and 2086 (see FIGS. 1B and 3).
[498] While ORF 4431 was the most potent protein identified in the fractions, mouse antibodies against recombinant lipidation 4431 were not bactericidal and did not provide a protective response in animal models. Further analysis of ORF 5163 is in progress.
[499] The second most potent component of the formulations described herein corresponded to the product of ORF 2086.
[500] Immunogenicity method:
[501] Antiserum Manufacturing:
[502] Except where noted, protein compositions / vaccines were prepared with 25 μg total protein and supplemented with 20 μg QS-21. 0.2 mL doses were administered at weeks 0 and 4 by sublingual (Lump) injection to female Swiss-Webster mice 6-8 weeks of age. Blood was collected at weeks 0 and 4, and final blood collection was performed at week 6.
[503] Sterilization Analysis:
[504] Bactericidal assays were performed essentially as described in the literature (see Mountzouros and Howell, 2000, J. Clin. Microbiol. 38 (8): 2878-2884). Complement-mediated antibody-dependent sterile titers to SBA were expressed as the reciprocal of the maximum dilution of test-serum that killed at least 50% of the target cells introduced into the assay (BC ₅₀ titers).
[505] Method used for 2086 protein identification:
[506] Cyanogen Bromide Cleavage and Direct Sequencing of Fragments:
[507] Cyanogen bromide cleavage of anion exchange nonadsorbed fraction (AEUF). AEUF was precipitated with 90% cold ethanol and dissolved in 10% / mL of cyanogen bromide in 70% formic acid to a protein concentration of 1 mg / mL. The reaction was carried out overnight at room temperature in the dark. The cleaved product was dry precipitated by speed vacuum and the pellet was dissolved in HE / 0.1% reduction TX-100. After SDS-PAGE, the components of the fractions were identified using N-terminal amino acid sequencing.
[508] Protease digestion / reverse phase / N-terminal sequencing for component identification
[509] AEUF was digested with GluC (V8), LysC or ArgC. The ratio of protein to enzyme was 30 μg: 1 μg (protein: enzyme). The decomposition reaction was performed overnight at 37 ° C. The digested protein mixture (30 μg) was passed through a 7 μm Aquapore RF-300 column, eluted with a 10-95% gradient of acetonitrile in 0.1% trifluoroacetic acid and the peaks collected manually. Blanks without protein were also performed and the peaks obtained therefrom were subtracted from the sample chromatogram. Peaks that occur only during the sample run were analyzed by mass spectrometry and samples with clear mass were analyzed by sequencing the amino acid N-terminus.
[510] N-terminal amino acid sequencing:
[511] For bands cut from blots, protein samples were transferred from SDS gels to PVDF membranes, stained with Amido Black (10% acetic acid in deionized water, 0.1% amido black) and bleached in 10% acetic acid. . Preferred protein bands were cut from 10 lanes using a scalpel or Mini-Exacto knife washed with methanol and placed in the reaction cartridge of an Applied Biosystems 477A protein sequencer. In order to sequence the samples directly in solution, Prosorb cartridges were collected and PVDF was wetted in 60 μl of methanol. PVDF was washed with 50 μl of deionized water and samples (50 μl) were loaded into PVDF. After washing the sample with 50 μl of deionized water, the probe PVDF was punched out, dried and placed in the reaction cartridge of the Applied Biosystems 477A Protein Sequencer. In both methods, the Applied Biosystems 477A protein sequencer is operated for at least 12 cycles (1 cycle: blank, 1 cycle: standardization, 10 or more cycles: identification of preferred residues) under optimal blot conditions, and the Applied Biosystems 120A PTH PTH-amino acids were detected on the analyzer. Periods were collected on both analog chart recorders and digital software instruments. Amino acids were assigned by comparing the retention time on their respective analyzers with a standard set of PTH-amino acids using analog and digital data (cysteine residues were destroyed and not detected during conversion). Multiple sequence information could be obtained from a single residue, and first-to-secondary assignments were made based on signal strength.
[512] LC-MS / MS
[513] Protein samples purified by IEF were further analyzed by SDS-polyacrylamide gel electrophoresis. Proteins are visualized by Coomaasie blue staining, the bands of interest are manually cut, separated, alkylated and trypsin (Promega, Promega, in situ) using an automated in-gel trypsin digestion robot (1). Madison, WI). After digestion, the peptide extracts were concentrated to a final volume of 10-20 μl using a Savant Speed Vac Concentrator (ThermoQuest; Holdbrook, NY).
[514] Peptide extracts were analyzed on automated microelectrospray reversed phase HPLC. Briefly, the boundary area of a microelectrospray consisting of a Picofrit fused silica spray needle, 50 cm long with 75 μm ID, and 8 μm orifice diameter (New Objective; Cambridge, Mass.) Filled with μm C18 reverse phase beads (YMC, Wilmington, NC) to 10 cm length. The picoprit needle was mounted on a fiber lens holder (Melles Griot; Irvine, CA) attached to a home-built base located in front of the mass spectrometer detector. The rear of the column was sealed with lead through titanium coalescing to provide an electrical connection to the electrospray boundary area. Fused Silica Capillary (FSC) Piped Merge to FAMOS Autosampler (LC-Packing; San Francisco, CA) Connected to HPLC Solvent Pump (ABI 140C, Perkin-Elmer, Norwalk, CT) Connected with. HPLC solvent pumps were delivered at a flow rate of 50 μl / min (reduced to 250 nL later) using a peak microtight splitting tee (Upchurch Scientific; Oak Harbor, WA) In addition, the FSC transmission line was used to transfer to an automatic sampler. Both the LC pump and autosampler are each adjusted using their internal user program. Samples were inserted into a plastic autosampler tube, sealed and injected using a 5 μl sample loop.
[515] Microcapillary HPLC-Mass Spectroscopy:
[516] Peptides extracted from degradation in the gel were separated by microelectrospray using a 50 minute gradient of 0-50% solvent B (A: 0.1 M HoAc, B: 90% MeCN / 0.1 M HoAc). Peptides were analyzed using capillaries heated to 150 ° C. on a Finnigan LCQ ion trap mass spectrometer (ThermoQuest, San Jose, Calif.) Operating on a 1.5 kV spray bolt. Data was acquired by automatic MS / MS method using the data acquisition software provided with the instrument. Acquisition methods include scanning the top three samples with the most ions in the MS scan after 1 MS scan (375-1200 m / z). Dynamic extraction and isotope extraction were used to increase the number of peptides analyzed (conditioning: 3 amu = extraction width, 3 minutes = extraction time, 30 seconds = pre-extraction time, 3 amu = isotope extraction width). . Automated analysis of MS / MS data (from Sanger). This was done using the SEQUEST computer algorithm included in the Finigan Biowork Data Analysis Package (ThermoQuest, San Jose, CA) using a database of proteins derived from the complete gene of Meningitidis. The results of the study are shown in FIG. 3.
[517] Example 2
[518] Cloning of Recombinant Lipidation P2086 (rL2086)
[519] A) natural leader sequence
[520] Source Material:
[521] ORF 2086 was amplified by PCR from clinical isolates of serogroup B Neisseria menigitidis strains called 8529. Serum groups, serotypes and serosubtypes of this strain are shown in parentheses; 8529 (B: 15, P1: 7b, 3). This meningococcal strain was obtained from RIVM, (Bilthoven, The Netherlands). The mature 2086 protein gene sequence of meningococcal strain 8529 is provided herein as SEQ ID NO: 212.
[522] PCR amplification and cloning methods:
[523] Visual observation of ORF 2086 indicates that this gene has a potential lipoprotein signal sequence. Additional analysis using the trademark Hidden Markov Model Lipoprotein algorithm confirmed that ORF 2086 contains lipoprotein signal sequences. In order to recombinantly express P2086 in a more natural form, oligonucleotide primers were designed to amplify the full-length gene comprising the lipoprotein signal sequence, wherein the primers were en. Based on Sanger's sequence analysis for Meningitidis A ORF 2086 (5 'Primer-CT ATT CTG CAT ATG ACT AGG AGC and 3' Primer-GCGC GGATCC TTA CTG CTT GGC GGC AAG ACC; SEQ ID NO: 304 respectively (Compound No.) 4625) and SEQ ID NO: 303 (Compound No. 4623) (see Table IV herein)). Yen 2086 gene. Amplification was carried out from Meningitidis strain 8529 by polymerase chain reaction (PCR) [ABI 2400 thermal cycler, Applied Biosystems, Foster City, CA]. The product amplified to the correct size was ligated and cloned into pCR2.1-TOPO (Invitrogen). Plasmid DNA was restriction digested with NdeI and BamHI and the gel was purified and ligated to the pET-27b (+) vector (Novagen).
[524] Oligonucleotide primers described herein were synthesized on a PerSeptive Biosystem oligonucleotide synthesizer using β-cyanoethylphosphoramidite chemistry (Applied Biosystems, Foster City, Calif.). Primers used for PCR amplification of the ORF 2086 gene family are listed in Table IV (primers of the invention are not limited to the examples of the following primers).
[525]
[526] RLP2086 lipoprotein expression using native leader sequences
[527] As shown in FIG. 5, plasmid pPX7340 was transformed / transfected or infected with BLR (DE3) pLysS host cells (Life Sciences). One transformant was selected and inoculated into 50 mL of terripic broth containing 2% glucose, kanamycin (30 μg / mL), chloramphenicol (30 μg / mL) and tetracycline (12 μg / mL). Overnight cultures were diluted with 1 L of territorial broth containing 1% glucose and the same antibiotic. The starting OD ₆₀₀ value was 0.4. After 2 hours the OD ₆₀₀ was 0.6 and a sample was taken before induction. Cells corresponding to an OD ₆₀₀ value of 1 were centrifuged and the supernatant was removed. Whole cell pellet was resuspended in 150 μl Tris-EDTA buffer and 2 × SDS-PAGE sample buffer. IPTG was added at a final concentration of 1 mM. After 3.5 hours post induction samples were taken as described and analyzed on SDS-PAGE (see FIG. 4).
[528] Purification of rLP2086:
[529] This rLP2086 by differential detergent extraction. Solubilized from E. coli. Unlike P2086 in the natural environment, rLP2086 was not significantly dissolved by Triton X-100 or Zwittergent 3-12. Bulk of rLP2086 was solubilized with sarcosyl (indicating that rLP2086 interacts with the outer membrane component of E. coli differently from the outer membrane component of N. meningitidis). Dissolved rLP2086 is contaminated with many Purification similar to the natural protein in E. coli, it could be removed by adsorption on an anion exchange resin at pH 8. Although the pH unit exceeded the theoretical pi above 1.5, rLP2086 remained unadsorbed at pH 8. rLP2086 was further purified by adsorption on a cation exchange resin at pH 4.5.
[530] Homogeneity of rLP2086 according to SDS-PAGE is shown in FIG. 2. The mass of rLP2086 was measured by a Maldi-TOF mass spectrometer and found to be 27,836. This mass value differed from the theoretical mass of 27,100 by 736 (this value is almost similar to the mass of the N-terminal lipid modification form common to bacterial lipoproteins). Both natural protein and rLP2086 have been shown to be envelope membrane lipoproteins. Sequencing attempts at the N-terminus were blocked, consistent with modifications at the end.
[531] Purification Method:
[532] Frozen pellets of BLR DE3 pLysS cells expressing P2086 were 20 mL / g in 10 mM HEPES-NaOH / 1 mM EDTA / 1 μg / mL Pefabloc SC protease inhibitor (Roche) pH 7.4 (HEP) Resuspend in wet cell weight and thaw by microfluidizer (microfluidics Corporation Model 110 Y). Cell lysis was centrifuged at 150,000 × g for 1 hour. The pellet was washed twice with HEP, centrifuged twice and the resulting membrane pellet was frozen overnight. The pellet was dissolved for 30 minutes with 10 mM HEPES-NaOH / 1 mM MgCl ₂ /1% TX-100 (pH 7.4) and then centrifuged at 150,000 × g for 30 minutes. This was repeated three times. Membrane pellets were washed two more times with 50 mM Tris-HCl / 5 mM EDTA / 1% Zwittergent 3-12 (pH 8) as above, followed by 50 mM Tris-HCl / 5 mM EDTA / 1% Wash twice with Vitergent 3-14 (pH 8) and 50 mM Tris-HCl / 5 mM EDTA / 1% Zwittergent 3-14 / 0.5 M NaCl (pH 8).
[533] rLP2086 was dissolved in 50 mM Tris-HCl / 5 mM EDTA / 1% sarcosyl (pH 8). This sarcosyl extract was adjusted to 1% Zwittergent 3-14 (Z3-14) and dialyzed twice for 30-fold excess of 50 mM Tris-HCl / 5 mM EDTA / 1% Z3-14 (pH8) It was. The dialyzed rLP2086 extract was precipitated with 90% ethanol to remove remaining sarcosyl and dissolved in 50 mM Tris-HCl / 5 mM EDTA / 1% Z3-14 (pH8) (TEZ). Insoluble material was removed by centrifugation, the supernatant was passed through an anion exchange chromatography column, and rLP2086 was collected in unbound fractions. Unbound material was dialyzed twice against a 30-fold excess of 25 mM NaAc / 1% Z3-14 (pH 4.5) and passed through a cation exchange chromatography column. rLP2086 was eluted with a NaCl 0-0.3 M gradient and analyzed by SDS-PAGE (Coomassie staining). The rLP2086 collection solution was determined to be 84% pure by laser concentration method.
[534] Surface Reactivity and Bactericidal Activity of Antiserum against rLP2086 Subfamily B
[535] As shown in Table VII, purified rLP2086 from subfamily B strain 8529 showed surface reactivity against all 10 2086 subfamily B strains tested by whole-cell ELISA. Bactericidal activity was measured against 9 of 10 2086 subfamily B strains expressing heterologous serosubtype antibodies (PorA). These strains are representative strains causing serogroup B meningococcal disease throughout Western Europe, the Americas, Australia and New Zealand. Only strains (870227) that did not die in sterile assays reacted strongly with anti-rLP2086 (subfamily B) serum by whole-cell ELISA (which indicates that this strain expresses proteins with epitopes common to P2086).
[536] The surface reactivity of the 2086 subfamily A strains listed in Table VII was also tested by whole cell ELISA. Very low levels of reactivity were observed in two of these three strains (which indicates that some 2086 subfamily A strains may not cross react with antibodies generated against rLP2086 subfamily B). PCR amplification methods also used to identify 2086 subfamily B genes from strain 8529 were performed on strains 870446, NMB and 6557. 2086 No PCR amplification products of subfamily B were detected.
[537] Immunogenicity Method
[538] Antiserum Manufacturing:
[539] The vaccine was prepared as described in Example 1. However a 10 μg dose was used.
[540] Whole Cell Enzyme-linked Immunosorbent Assay (ELISA):
[541] yen. The whole cell suspension of meningitidis was diluted in sterile 0.01 M phosphate, 0.137 M NaCl, 0.002 M KCl (PBS) to have an optical density of 0.1 at 620 nm. 0.1 mL of the suspension was added to each well of a Nunc Bac T 96 well plate (Cat # 2-69620). The cells were dried at room temperature for 3 days on a plate, then the surface was covered and stored upside down at 4 ° C. Plates were washed with buffer (0.01 M Tris-HCl, 0.139 M NaCl / KCl, 0.1% dodecylpoly (oxyethyleneglycoether) _n (n = 23) (Brij-35®, ICI Americas Inc. (Americas , Inc.), Wilmington, commercially available from Delaware, pH 7.0-7.4) Anti-serum dilutions were prepared in PBS, 0.05% Tween-20 / azido, 0.1 mL of which were coated The plates were incubated for 2 hours at 37 ° C. The plates were washed three times with wash buffer Chlorine-anti-mouse IgG AP (Southern Biotech) in PBS / 0.05% Tween-20 1: Dilute at a rate of 1500, add 0.1 mL to each well, and incubate the plate for 2 hours at 37 ° C. The plate was washed (as above) The substrate solution was p-nitrophenyl phosphate (Sigma; diluted Sigma) in 1 M diethanolamine /0.5 mM MgCl ₂ 1 mg / mL Substrate was added to the plate at 0.1 mL per well and incubated for 1 hour at room temperature The reaction was stopped with 50 μl / well of 3 N NaOH and the plate was read at 405 nm with reference at 690 nm as reference. It was.
[542] B) P4 leader sequence:
[543] PCR amplification and cloning methods:
[544] To optimize rLP2086 expression, the 2086 gene was cloned after the P4 signal sequence of atypical Haemophilus influenza (Green et al., 1991). Primers used for lipoprotein cloning are listed in Table IV and represented by compound numbers (5658, 5660, 6473, 6543 and 6385). yen. ORF 2086 from Meningitidis B strain was amplified using primers (Compound Nos. 5658 and 5660). yen. ORF 2086 from Meningitidis serogroup B strain CDC 1573 was amplified using primers (Compound Nos. 6385 and 5660). yen. ORF 2086 from Meningitidis serogroup B strain 2996 was amplified using primers (Compound Nos. 6473 and 6543). N-terminal (5 ') primers were designed to be homologous to the mature region of the 2086 gene (starting at the serine residue at amino acid position 3 immediately downstream of cysteine). A BamHI cleavage site (GGATTC) was incorporated at each N-terminal primer 5 'end to insert a glycine residue at amino acid position 2 of the mature protein. The C-terminal (3 ') primer was designed to be homologous to the C-terminal end of the 2086 gene, which included the stop codon as well as the SphI site for cloning. Each yen. Fragments amplified from Meningitidis B strains were cloned into intermediate vectors and screened by sequencing.
[545] Plasmid DNA from the correct clone was digested with BamHI and SphI restriction enzymes (New England Biolabs (NEB)). The vector designated pLP339 (supplied by the applicant's assignee) was selected as the expression vector. This vector uses the pBAD18-Cm template (Beckwith et al., 1995) and contains the P4 lipoprotein signal sequence and the P4 gene of atypical Haemophilus influenza (Green et al., 1991). The pLP339 vector was partially digested with restriction enzyme BamHI and then digested with SphI. Amplified 2086 fragments (BamHI / SphI) were each independently ligated to the pLP339 vector (partial BamHI / SphI). This cloning method places the mature 2086 gene behind the P4 lipoprotein signal sequence. The BamHI site remains at the cloning junction between the P4 signal sequence and the 2086 gene (see plasmid construct shown in FIG. 7). The following is an example of a sequence located at the BamHI cloning junction:
[546] [P4 signal sequence] -TGT GGA TCC- [rest mature 2086 nucleic acid sequence]
[547] [P4 signal sequence] -Cys Gly Ser- [rest mature 2086 amino acid sequence]
[548] As shown in FIG. 7, each amplified fragment was cloned into a pBAD18-Cm vector containing a P4 leader sequence. recombinant E. coli expressing rP4LP2086 (recombinant P4 lipidation 2086) Fermentation on E. coli BLR pPX7343 attempted to increase cell density by addition of glucose. The fermentor was filled with 10 L complete M9 minimal medium supplemented with 1% glucose.
[549] The initial glucose concentration of the fermenter was 45 g / L. The fermenter was incubated with a starting OD value of 0.25. Additional 20 g / L glucose was added when the OD value was about 25. When glucose was depleted at OD value 63.4 of the culture, it was induced with 1% arabinose. It was fermented up to 3 hours after induction. Samples were stored separately at 0, 1, 2 and 3 hours after induction and quantified using BSA. At 3 hours 0.35 g / L protein and 7% total cytoplasmic protein were obtained. A total of 695 g of wet cell paste was harvested from 10 L of culture.
[550] rP4LP2086 was purified in the same manner as described in paragraph A of Example 2 above.
[551] Example 3
[552] Developmental Genetics for Non-lipidated Mature 2086 Proteins
[553] To further assess the immunogenicity of the 2086 protein, cloning and expression of non-lipidated P2086 was performed.
[554] PCR gene amplification of ORF 2086:
[555] Oligonucleotides used for PCR amplification of non-lipidated 2086 genes are listed in the primer table of Table IV. The 2086 gene of the 8529 strain could be amplified with primers of Compound Nos. 5135 and 6406 (SEQ ID NOs. 308 and 312, respectively) as shown in the table. The 2086 gene from the CDC1573 strain could be amplified with primers of compound numbers 5135 and 6474 (SEQ ID NOs: 308 and 316, respectively). 2086 genes from the 2996 strain could be amplified with primers of compound numbers 6404 and 6605 (SEQ ID NOS 312 and 320, respectively).
[556] The characteristic of these primers is that there is a synthetic BglII cleavage site in each primer, a synthetic NdeI cleavage site in compounds No. 6404 and 6474 and a termination codon in all three reading frames in compound nos. 5135 and 6605. . Compound Nos. 6404 and 6474 primers amplify a 2086 gene in which ATG (Met), which replaces a mature 2086 polypeptide with a single amino acid (TGC Cys substitution), is fused to a second amino stop codon (ACG).
[557] PCR cloning vector was TOPO-PCR2.1 (Invitrogen, Valencia, CA).
[558] The vector used to express the non-lipidated 2086 protein was pET9 from Novagen (Madison, WI).
[559] this. E. coli cloning strain was Top10 (Invitrogen, Carlsbad, CA).
[560] this. E. coli expressing strain was BLR (DE3) pLysS (Novazen, Madison, Wis.).
[561] The culture medium for cloning purposes was a terrypic broth liquid or agar with glycerol (according to Sambrook et al.) Replaced with 1% sterile glucose and containing the appropriate antibiotic (ampicillin or kanamycin).
[562] Plasmids were purified with Qiagen Spin Miniprep Kit (Valencia, Calif.).
[563] Preparation of Production Strains or Cell Lines for Non-lipidized 2086 Expression:
[564] The 2086 gene was amplified by polymerase chain reaction (PCR) (AmpliTaq and ABI 2400 thermal rotator, Applied Biosystems, Foster City, CA) from chromosomal DNA derived from meningococcal strain 8529. Oligonucleotide primers represented by compound numbers 6474 and 5135 (SEQ ID NOs: 316 and 308, respectively) were used in each reaction when amplifying the 2086 gene by PCR. The amplified 2086 PCR product was cloned directly into the TOPO-PCR2.1 cloning vector and selected on terry broth agar supplemented with 100 μg / ml ampicillin and 20 μg / ml X-Gal. White colonies were selected and grown. Plasmid DNA was purified using Qiagen Miniprep Kit and plasmids were screened for PCR fragment insertion. PCR insert plasmids were DNA sequenced (Big Dye chemistry on ABI377 sequencer, Applied Biosystems, Foster City, CA).
[565] Plasmids showing the correct DNA sequence were digested with BglII restriction enzymes and BglII fragments were gel purified using the GeneClean II Purification Kit (Bio101, Carlsbad, Calif.). Purified BglII fragment was cloned into the BamHI site of the expression vector pET9a. pET9a / 2086 clones were selected on terry broth plates supplemented with 30 μg / ml kanamycin. Kanamycin resistant clones were grown and miniprep plasmid DNA was purified. Plasmids were screened for 2086 genes with proper orientation at the BamHI site. Plasmids with the correct orientation indicate that the T7-antigen was fused to the amino terminus of the 2086 gene (rP2086T7). This fusion rP2086T7 gene was transformed into BLR (DE3) pLysS, selected on terry broth / Kan plates, incubated in terry broth, 1 mM IPTG (isopropyl-D-thiogalactopyranoside) RP2086T7 fusion protein expression was induced. rP2086T7 fusion protein was expressed at high levels.
[566] These fusion plasmids were then restriction digested with NdeI to delete the T7-antigen and connect the mature 2086 gene directly to the ATG start site provided by the vector. Plasmids lacking the NdeI site were transformed into Top 10 cells and selected on Terrific Broth / Kan plates. Candidate clones were grown and miniprep plasmid DNA was purified. Plasmid DNA was sequenced to confirm deletion and integrity of the 2086 gene sequence. Plasmids are represented by plasmid maps called pPX7328 (FIG. 6). Plasmids showing the correct DNA sequence were transformed into BLR (DE3) pLysS, selected on terry broth / Kan plates, grown in terry broth, and induced 2086 protein expression with IPTG. When the T7-tag was removed, the pET9a vector failed to express mature 2086 protein in strain BLR (DE3) pLysS.
[567] Non-lipidated 2086 Protein Production:
[568] Purified plasmid DNA was used to transform the expression strain BLR (DE3) pLysS. BLR (DE3) pLysS cells with plasmids were resistant to kanamycin and were able to induce high levels of PorA protein expression with the addition of 1 M IPTG. rP2086T7 fusion protein. Insoluble inclusion bodies in E. coli cell line BLR (DE3) pLysS could be expressed at ˜40% level of total protein. Purified fusion proteins were used to immunize mice and produced significant levels of bactericidal antibodies against heterologous meningococcal strains (see Table V).
[569] 2086 non-lipidation gene mutagenesis:
[570] PCR primer mutagenesis was performed at the 5 'end of the 2086 gene. Expression studies were performed under the method measured by removing the T7-tag while mature rP2086T7 was expressed at high levels.
[571] Non-lipidated rP2086T7 Tablets:
[572] E. expressing non-lipidated rP2086T7. E. coli BLR (DE3) pLysS cells were lysed by microfluidizer in 10 mM Hepes-NaOH / 5 mM EDTA / 1 mM Pepablock SC (pH 7.4). Cell lysis was then centrifuged at 18,000 × g for 30 minutes. Inclusion body pellets were washed three times with 50 mM Tris-HCl / 5 mM EDTA / 1% Triton X-100 (pH 8), followed by centrifugation at 24,000 x g for 30 minutes at each time point. Inclusion body pellets were washed twice with 50 mM Tris-HCl / 5 mM EDTA / 1% Zwittergent 3-14 (pH 8) and then centrifuged at 24,000 x g for 15 minutes at each time point. Inclusion body pellets were dissolved in 50 mM Tris-HCl / 5 mM EDTA / 4 M urea (pH 8) for 2 hours and then centrifuged to remove insoluble matter. Supernatants (dissolved rP2086T7) were dispensed into four identical samples. One sample was adjusted to 50 mM Tris-HCl / 5 mM EDTA / 250 mM NaCl / 2 M urea (pH 8) (excluding detergent) and one was 50 M Tris-HCl / 5 mM EDTA / 250 mM NaCl / 2 Adjusted with M urea / 1% hydrolyzed Triton X-100 (pH8) (TX-100), one was 50 mMTris-HCl / 5 mM EDTA / 250 mM NaCl / 2 M urea / 1% Zwittergent 3- 12 (pH 8) (Z3-12) and using the stock solution 50 mM Tris-HCl / 5 mM EDTA / 250 mM NaCl / 2 M urea / 1% Zwittergent 3-14 (pH 8) (Z3 -14). To remove urea, samples were completely dialyzed against each buffer containing no urea. The samples were then dialyzed completely against each buffer containing urea and 60 mM NaCl to reduce NaCl concentration. Insoluble material was removed by centrifugation at 2,000 x g for 15 minutes and the resulting supernatant (refolded rP2086T7) was used for further experiments. The homogeneity of rP2086T7 was found to be 91-95% as measured using Coomassie stained SDS-PAGE and laser densitometry.
[573] Immunogenic Methods-As Described in Example 2
[574] Purified fusion proteins were used to immunize mice and generated significant levels of bactericidal antibodies against heterologous meningococcal strains (see Table V below):
[575]
[576] Example 4
[577] Generation of ORF 2086 Chimeric Clones
[578] The N-terminal region of strain CDC-1573 2086 gene comprises repeated fragments not present in strains 8529 and 2996 (see FIG. 8). This repeated fragment has two teeth. It has been shown to increase recombinant 2086 protein expression levels from E. coli based expression systems (pET and pBAD). Recombinant protein expression levels from the CDC-1573 2086 gene in the pET and pBAD expression systems were significantly higher than recombinant expression levels from the 2086 genes of strains 8529 and 2996 using the same system. The 2086 gene N-terminal regions from all three strains were relatively homologous except for the repeating fragments above. Thus, it is reasonable to identify the CDC-1573 N-terminus with 2086 genes from strains 8529 and 2996, where the level of recombinant 2086 protein expressed from these genes will increase when using the pET and pBAD systems. .
[579] Material and method:
[580] Chromosomal DNA from strains 8529 and 2996 were purified and used as template for PCR amplification of the chimeric 2086 gene. PCR primers of SEQ ID NOs: 6721 and 5135 (SEQ ID NOs: 321 and 308, respectively) were used to amplify the chimeric 2086 gene from strain 8529, and PCR primers of Compounds 6721 and 6605 (SEQ ID NOs: 321 and 320, respectively), chimeric from strain 2996. 2086 gene was used to amplify. PCR products were cloned directly into Invitrogen's PCR2.1 TOPO vector and then screened by DNA sequencing to identify intact chimeric 2086 genes. The gene was then digested with BglII from the PCR2.1 vector and the BglII fragment inserted into the BamHI site of the pET9a plasmid. Plasmid insertions were screened for appropriate orientation and then digested with NdeI. Linear NdeI fragments were self-ligated to delete small NdeI fragments containing the T7-tag sequence provided by the pET9a vector. The deletion directly linked the T7 promoter to the 5 'end of the chimeric 2086 gene. An NdeI deleted plasmid. E. coli strain BL21 (DE3) was transformed and kanamycin resistant colonies were screened for IPTG induced chimeric 2086 protein expression.
[581] In the first study, the chimeric 2086 gene of strain 2996 was found to express about twice as much recombinant protein as the native 2996/2086 gene expressed in the pET9a system. The pBAD system has not been tested yet.
[582] Although only one experiment was performed, the data indicate that there is increased utility from the chimeric 2086 gene. CDC-1573 N-terminal fusion to the 2086 genes of strains 8529 and 2996 provide increased recombinant 2086 protein expression.
[583] Example 5
[584] yen. 2086 PCR Screening of Meningitidis Strains:
[585] To determine the conservation of 2086 genes among clinical isolates, 88 yen. PCR amplification was performed in Meningitidis strains.
[586] Initial PCR identification of ORF 2086 used the primers set forth in Table IV (see Example 2 above), identified by Compound Nos. 4623, 4624 and 4625 (SEQ ID NOs: 303, 304 and 305, respectively). These primers are in Sanger N. It was named based on the meningitidis serogroup A sequence. To facilitate screening for multiple strains, internal primers for the 2086 gene were designed. 88 yen in total. Meningitidis strains were screened by PCR with newly designed internal 2086 primers identified as compounds Nos. 5005 and 5007 (SEQ ID NOs: 306 and 307). Using these primers, we found that 63 of 88 (about 70%) of N. et al. 2086 genes could be identified from Meningitidis strains (see Table VI-A).
[587] Yen of Sanger. Meningitidis serogroup A sequence and TIGR. The extended region surrounding the 2086 gene in the Meningitidis serogroup B sequence was examined and aligned. Primers were designed to correspond to the upstream and downstream regions of the 2086 gene. The purpose is various yen. These primers were used to compare sequences by amplifying a wider portion from the Meningitidis strain than the full length 2086 gene. PCR amplification of one strain (6557) using Compound Nos. 6470 and 6472 (SEQ ID NOs. 313 and 314, respectively) showed low yields of amplification products. The product amplified using strain 6557 was cloned and plasmid DNA was sequenced. As a result, a new type of 2086 gene has been identified that has greater sequence variability than previously known sequence variability. The 2086 gene from strain 6557 was about 75% identical at the amino acid level with other strains sequenced. Interestingly, strain 6557 was one of 30% of the strains previously tested negative by 2086 PCR screening described above.
[588] Internal primers specific for the C-terminal variable region inside strain 6557 were designed. These primers were used to screen more variable 2086 genes in about 30% of the strains previously tested negative by 2086 PCR screening. All available yen. Meningitidis strains (n = 88) were screened by PCR using the newly identified internal 2086 primers (Compound Nos. 6495 and 6496; identified by SEQ ID NOs: 159 and 160, respectively). About 30% yen previously tested negative by PCR for 2086. Only Meningitidis strains were PCR positive in this screening. The set of genes amplified from the strains that were previously PCR negative (about 30%) represent a new type of 2086 gene or a second group of 2086 genes, which we named 2086 subfamily A. The set of 2086 genes amplified from about 70% of the strains using primers from 8529 was named subfamily B herein.
[589] Subfamily A of the 2086 gene is illustrated by, but is not limited to, an odd numbered sequence of SEQ ID NOs: 1-173. Subfamily B of the 2086 gene is illustrated by, but is not limited to, an odd numbered sequence of SEQ ID NOs: 175-251.
[590] Yen used for PCR amplification studies. Meningitidis strains were selected from Tables VI-A and VI-B. The strains listed in the table above are yen. Although shown as an example of meningitidis strain, it is not limited thereto. The strains listed in Table VI-A are classified as 2086 protein subfamily A, and the strains listed in Table VI-B are classified as 2086 protein subfamily B. The strains listed in each table are classified by serotypes. Strains available from four sources are listed in the table: MPHL-Manchester Public Health Laboratory, Manchester, UK; RIVM (Bilthoven, The Netherlands); University of Iowa, College of Medicine, Department of Microbiology, Iowa City, IA; And Walter Reed Army Institute of Research, Washington, D.C.
[591]
[592]
[593]
[594] Other strains are readily available as isolates from infected individuals.
[595] Example 6
[596] Reactivity of rLP2086 antiserum against meningococcal strains:
[597] Table VII below shows the cross-reactivity and cross protection of rLP2086 described above. As indicated in the table, rLP2086 was processed and analyzed using a variety of techniques including whole cell ELISA (WCE) titer, bactericidal assay (BCA), and juvenile rat (IR) assay, resulting in polyclonal antibodies directed against 2086 protein. The bacterial cell surface reactivity of was measured.
[598]
[599] Example 7
[600] Various constructs were prepared for expressing ORF2086 protein. Table VIII below is a table of r2086 constructs that serve to show examples and illustrate the completion of the present invention, but the invention is not limited thereto.
[601]
[602] Example 8
[603] Further studies with outer membrane proteins depleted of LOS have identified additional strains that produce outer membrane protein (s) other than PorA that can induce bactericidal antibodies against strains expressing heterologous serotypes. The following describes additional studies to identify outer membrane lipoproteins that can reduce the number of additional proteins, particularly proteins required for meningococcal immunogenic compositions, in accordance with one embodiment of the present invention. This further study complements the studies described in the examples above.
[604] Subgroups of target proteins were identified using subcellular sorting, differential detergent extraction, isoelectric focusing, and ion exchange chromatography for immunization and bactericidal analysis of multiple strains. Direct sequence analysis of the principal component revealed that the N-terminus was blocked. Internal protein sequences were obtained by direct sequence analysis of polypeptides derived from chemical degradation and proteolytic degradation. The genome sequences of Group A meningococcal strains were downloaded from Sanger Centers and analyzed in Applicants' Bioinformatics group using existing and proprietary algorithms to create a searchable database. Peptide sequence data indicated that ORF2086 is the desired sequence. The P2086 gene was PCR from strain 8529 using this ORF based primer. Sequence analysis of the gene, the fact that the N-terminus was blocked, and its subcellular location indicated that P2086 was a lipidated outer membrane protein (LP2086). Variants from rLP2086-8529 and other meningococcal strains include E. coli. H in Coli. Recombinantly expressed as lipoproteins using the H. influenzae P4 signal sequence. These recombinant proteins differentiate this by detergent extraction. Isolated from E. coli membrane, purified using ion exchange chromatography, used for immunization of mice. Mouse anti-LP2086 sera produced several different serotypes. It was possible to promote bactericidal activity against Meningitidis strains. A large number of yen. Further analysis of the P2086 gene from Meningitidis strains revealed that these sequences belong to two groups named subfamily A and subfamily B (see FIG. 12). Antisera generated against subfamily B protein showed bactericidal activity against nine strains expressing subfamily B protein and bactericidal activity against one strain expressing subfamily A protein. Subfamily A antiserum showed bactericidal activity against subfamily A strains. A mixture of one rPorA and one rLP2086 induced complementary antibodies in the extended vaccine range beyond the vaccine range induced by only one protein.
[605] This observation leads to the following results. The rLP2086 antigen can induce bactericidal antibodies against meningococcal strains expressing heterologous PorA and heterologous P2086 proteins. The P2086 antigen family may be a useful vaccine or immunogenic either alone or in combination with other Neisseria antigens.
[606] Hereinafter, the study will be described in detail. Complex mixtures of soluble outer membrane proteins (sOMPs) have been shown to induce PorA independent bactericidal antibodies against strains expressing heterologous PorA proteins. Mouse immunizations following differential detergent extraction, isoelectric focusing and ion exchange chromatography methods were used to accompany immunologically active ingredients.
[607] At each stage, serum was analyzed for surface reactivity and bactericidal activity against several strains containing serosubtype antigens representative of the global epidemiology of meningococcal disease.
[608] Group B yen using this isolation and immunization method. Novel cross-reactive immunogenicity candidates for meningitidis were identified.
[609] Generation of PorA Deficient Strains—The porA chromosome locus from strain 2996 was cloned into plasmid pPX7016. In the plasmid, the porA promoter, S / D box and the first 38 N-terminal codon were deleted and replaced with a self-suppressing KanR expression cassette. This plasmid was linearized with restriction enzymes and serotype strain PI: 5,2; PI: 9; PI: 7,16; PI: 15; PI: 4; It was naturally transformed to PI: 3 and PI: 10. Kanamycin resistant transformants were selected and screened for loss of PorA by serotype specific monoclones in ELISA.
[610] Bactericidal analysis: Mountzourous, KT and Howell, AP Detection of Complement-Mediated Antibody-Dependent Bactericidal Activity in a Flourescence-Based Serum Bactericidal Activity for Group B Neisseria meningitidis . J Clin Microbiol. 2000; 38: 2878-2884.
[611] Whole Cell Enzyme Linked Immunosorbent Assay (ELISA): N. Meningitidis whole cell suspension was diluted in sterile 0.01 M phosphate, 0.137 M NaCl, 0.002 M KCl (PBS) to an optical density of 0.1 at 620 nm. 0.1 mL of this suspension was added to each well of a Nunc Bac T 96 well plate (Cat # 2-69620). Cells were dried overnight at 37 ° C. on plates, inverted and stored at 4 ° C. Plates were washed three times with wash buffer (0.01 M Tris-HCl, 0.139 M NaCl / KCl, 0.1% Brij-35, pH 7.0-7.4). Dilutions of antiserum were prepared in PBS, 0.05% Tween-20 / azide, and 0.1 mL was transferred to coated plates and incubated at 37 ° C. for 2 hours. Plates were washed three times with wash buffer. Goat-anti-mouse IgG AP (Southern Biotech) was diluted 1: 1500 in PBS / 0.05% Tween-20, 0.1 mL was added to each well, and the plates were incubated at 37 ° C. for 2 hours. Plates were washed (as above). Substrate solution was prepared by diluting p-nitrophenyl phosphate (Sigma) at 1 mg / ml in diethanolamine. Substrate was added to the plate at 0.1 mL per well and incubated for 1 hour at room temperature. The reaction was stopped with 500 μl / well of 3 N NaOH and plates were read at 405 nm with a 609 nm reference.
[612] Recombinant PorA Induction: BLR (DE3) / pET9a strains were incubated overnight at 37 ° C. in HySoy Broth (Sheffield Products) supplemented with Kan-30 and 2% glucose. In the morning the O / N culture was diluted 1/20 in HySoy Broth, Kan-30 and 1% glycerol and incubated at 37 ° C. for 1 hour. IPTG was added at a final concentration of 1 mM to induce expression in the culture. The culture was harvested after incubating for another 2-3 hours.
[613] Recombinant PorA Purification: Using 8 M urea, Lee. RPorA inclusion bodies from E. coli were solubilized and refolded by dialysis against buffer containing no urea. The refolded rPorA was then concentrated by diafiltration and the buffer exchanged to NaPO ₄ (pH 6) by G25 column. Dialysis rPorA was then run on a cation exchange column (S Fractogel) and diluted with 1M NaCl.
[614] SOMP from strain 8529 (P1.7-2,3) induced PorA independent bactericidal activity against strains expressing heterologous serosubtypes in mice. Table IX below shows bactericidal activity in the strains studied.
[615]
[616] Preparation of sOMP: yen. Meningitidis membranes were extracted with TX-100, Zwittergent 3-14 and Zwittergent 3-14 + 0.5 M NaCl. The above-mentioned sOMP was solubilized in Zwittergent 3-14 / 0.5 M NaCl extract. Extraction was performed using techniques known to those skilled in the art, such as those described in US Pat. No. 6,355,253, which is incorporated herein by reference.
[617] Immunogenicity: Female Swiss-Webster mice were immunized with 25 μg total protein immunized with 20 μg QS-21 at weeks 0 and 4. Blood collection and data analysis were performed at 6 weeks.
[618] 1: Bactericidal (BC ₅₀ ) titers are expressed as the reciprocal of the dilution of anti-serum that reduces the number of viable cells by 50%. Normal mouse serum at week 0 showed a BC ₅₀ titer of less than 25.
[619] 2: NST = unable to classify serotypes.
[620] Table X below shows a summary of purification and characterization of recombinant lipidated P2086 (rLP2086) for subfamily A and subfamily B.
[621]
[622]
[623] Refining Method: Count all variants using TX-100. Solubilized from E. coli membrane (exception: rLP2086-8529 solubilized with sarcosyl or urea). Further purification was achieved by combining anion exchange (TMAE), size exclusion and / or cation exchange (S Fractogel) chromatography in Tris-HCl or NaPO ₄ buffer.
[624] 1: Amino acid homology as compared to P2086 from strain 8529.
[625] 2: Purity by laser concentration measurement of colloidal Coomassie stained (simple blue stained) bands after SDS-PAGE.
[626] Immunogenicity of subfamily B member rLP2086-8529 was tested against homologous and heterologous strains.
[627] Table XII below shows the immunogenicity of rLP2086-8529, a subfamily B member tested against homologous and heterologous strains.
[628]
[629] Vaccination Procedures: Female Swiss-Webster mice 6-8 weeks old were immunized with 10 μg rLP2086-8529 and 20 μg QS-21 at weeks 0 and 4. Data analysis was performed at 6 weeks by blood collection.
[630] a: Amino acid homology of P2086 as compared to rLP2086-8529.
[631] b: Endpoint titer expressed as the inverse of dilution at absorbance = 0.1.
[632] c: BC ₅₀ titer expressed as the reciprocal of the dilution of anti-serum that reduces the viable cell number by 50%. Normal mouse serum at week 0 shows a BC ₅₀ titer of less than 10.
[633] Table XIII shows the immunogenicity of rLP2086-2996, a subfamily B member tested against homologous and heterologous strains.
[634]
[635] Vaccination Procedures: Female Swiss-Webster mice 6-8 weeks old were immunized with 10 μg rLP2086-2996 and 20 μg QS-21 at weeks 0 and 4. Data analysis was performed at 6 weeks by blood collection.
[636] a: Amino acid homology of P2086 as compared to rLP2086-2996.
[637] b: Endpoint titer expressed as the inverse of dilution at absorbance = 0.1.
[638] c: Bactericidal (BC ₅₀ ) titers expressed in reciprocal to dilution of anti-serum, which reduces the number of viable cells by 50%. Normal mouse serum at week 0 shows a BC ₅₀ titer of less than 10.
[639] Table XIV shows that antiserum is complementary to rLP2086 and rPorA when analyzing bactericidal activity by mixing rLP2086 and rPorA.
[640]
[641] Vaccination Procedures: Female Swiss-Webster mice 6 to 8 weeks of age were immunized with 10 μg rLP2086-8529 and 20 μg QS-21, or 15 μg rPorA and 100 μg MPL at weeks 0 and 4. Data analysis was performed at 6 weeks by blood collection.
[642] a: Bactericidal (BC ₅₀ ) titer expressed as the reciprocal of dilution of anti-serum, which reduces the number of viable cells by 50%. Normal mouse serum at week 0 shows a BC ₅₀ titer of less than 10.
[643] Table XV below shows that a mixture of rLP2086 subfamily and rPorA two induced bactericidal antibodies in mice.
[644]
[645] Vaccination Procedures: Female Swiss-Webster mice 6-8 weeks of age were immunized with 10 μg of protein and 20 μg of QS-21 at weeks 0 and 4. Data analysis was performed at 6 weeks by blood collection.
[646] a: Bactericidal (BC ₅₀ ) titer expressed as the reciprocal of dilution of anti-serum that reduces the number of viable cells by 50%. Normal mouse serum at week 0 shows a BC ₅₀ titer of less than 10.
[647] b: SfA-subfamily A, SfB-subfamily B
[648] c: appropriate monovalent control-rLP2086-8529, rLP2086-2996, rP1.5-1,2-2 or rP1.22-1,14-1 antiserum.
[649] The following is a summary of the results of the studies described above. Anti-rLP2086 antiserum showed bactericidal activity against 13 of 16 test strains. Eleven strains expressing different serotypes were killed by anti-P2086 sera. Bactericidal activity of anti-rLP2086 serum was complementary to anti-rPorA serum. A mixture of P2086 and PorA induced complementary bactericidal antibodies in mice. Differential vaccine extraction, purification, and immunization can be used to identify new vaccine candidates with functional antibody analysis for multiple strains. P2086 has been identified as a vaccine candidate capable of inducing bactericidal antibodies against strains that are heterologous to both P2086 and rPorA. Thus, proteins of the 2086 family can be useful vaccines alone or in combination with other Neisseria antigens.
[650] Example 9
[651] According to the above examples, additional meningococcal strains of various serogroups were screened by PCR for the presence of ORF 2086. Ultimately, 100 meningococcal strains were screened. This study and its overall results are described below. These results complement the data from the above examples.
[652] Two sets of internal PCR primers specific for the C-terminal variable region were used to identify subfamily A and B gene sequences. The presence of approximately 350 bp of PCR amplification product means that the 2086 gene sequence is present on the chromosome. All strains produced a single PCR product of expected size. Nucleotide sequences of 55 full-length ORF 2086 genes were determined, aligned (DNAStar MegAlign), and used to generate a phylogenetic tree (see FIG. 12).
[653] Nine of these 2086 genes were recombinantly expressed as rLP2086 lipoproteins in the pBAD arabinose inducible promoter system, and three of these genes were expressed as rP2086 non-lipidizing proteins in the IPTG inducible pET system. These recombinant proteins are Lee. Expressed in E. coli B. The purified recombinant protein was used to immunize mice and mouse antiserum was analyzed for its serum IgG titer and bactericidal activity against its various heterologous meningococcal strains.
[654] ORF 2086 was amplified by PCR from either meningococcal whole cells, purified chromosomal DNA or plasmid DNA templates.
[655] Nine of the ORF 2086 genes were cloned into the vector pLP339 to fuse the Haemophilus P4 leader sequence to the 5 'end of the ORF 2086 gene. this. E. coli strain BLR was used as a host strain for recombinant expression of the lipidated form of rP2086 from the pBAD / ORF 2086 clone (see FIG. 10A). The pBAD arabinose inducible promoter induces expression of the P4 signal / ORF 2086 fusion protein to express the lipidated form of rP2086. Three P2086 genes lacking a signal sequence were cloned behind the high activity T7 phage promoter of the pET9a vector. this. E. coli strain BL21 (DE3) was used as a host strain for recombinant expression of the non-lipidized form of ORF 2086 from a pET9a / ORF 2086 clone (see FIG. 10B). this. DE3 lysogen of E. coli strain BL21 can be induced to express T7 RNA polymerase under the control of the lacUV5 promoter by addition of IPTG (WCE; FEMS Micro. Lett., 48 (1987) 367-371 And [BCA; J. Clin. Microbiol., 38 (2000) 2878-2884].
[656] 55 different yens. The ORF2086 gene was cloned from the Meningitidis strain and sequenced. Nucleotide sequences were aligned (DNAStar MegAlign) and used to generate phylogenetic tree (see FIG. 12). This phylogenetic tree identified two subfamily of two distinct ORF 2086 gene nucleotide sequences. These two gene subgroups are similar at the 5 'end but contain significant variation near the 3' end. Although they appear to be very mutant, certain important regions of the gene are very homologous, even among different strains. Such conserved regions may provide functional continuity for the protein and may also be an indication of cross-protecting epitopes to be developed as vaccine targets.
[657] The 2086 gene was cloned from several serogroup B meningococcal strains and expressed in the presence and absence of lipidation signal sequences. 11A and 11B, gel photographs show E. coli expressing r2086 protein. Shows whole cell lysis of E. coli B. Non-lipidated forms fused to T7-tags were expressed at high levels. The T7-tag sequence can provide stability to the mRNA and significantly increase the level of translated polypeptide. This fusion protein appears to be deposited into inclusion bodies and can be easily purified and refolded using known protocols. The lipidated and non-lipidated forms of P2086 are expressed in approximately 5-8% of total cellular proteins, with the exception that rP2086 is expressed in approximately 50% of total proteins in the case of T7-tag fusions. The non-lipidated form of the protein appears to be soluble and located in the cytoplasm. The lipidated form of the protein appears to bind the membrane fraction and is solubilized using detergents.
[658] yen. Recombinant lipidated 2086 protein from Meningitidis B strain 8529 consistently induced higher serum IgG titers than the non-lipidized form (see Table XVI below), which was found in both homologous and heterologous meningococcal strains. Correlated with an increase in bactericidal activity levels (see Table XVII below). Natural lipidated forms of proteins may have a better four-dimensional structure for antigen presentation and / or attached lipids may act as adjuvants that stimulate greater immunogenic responses.
[659]
[660]
[661] The following description summarizes the results of the study. All yen tested. Meningitidis B strain appears to have one 2086-like gene. At least two 2086 gene families are shown: about 30% of subfamily A strains and about 70% of subfamily B strains. 55 yen. The 2086 gene was cloned from Meningitidis strains and sequenced. The sequence in subfamily A is about 86-100% identical at the DNA level. The sequence in subfamily B is about 89.5 to 100% identical at the DNA level. The sequences in subgroup A to subfamily B are about 60.9% to 74% identical at the DNA level. 2086 homologues were identified by PCR screening in the following strains:
[662] yen. Meningitidis A, B, C, W135, Y;
[663] yen. Lactamica; And
[664] yen. FA 1090 to Gonorhoea.
[665] Several ORF 2086 genes have been cloned and recombinantly expressed. The lipidated form of P2086 was expressed from nine meningococcal strains. These recombinant proteins were purified and used to vaccinate mice. The resulting antiserum is bactericidal.
[666] The non-lipidated form of P2086 was expressed from three of these nine strains. rLP2086 consistently elicits a larger immune response than rP2086. In addition, rLP2086 also shows enhanced bactericidal activity against both homologous and heterologous meningococcal strains.
[667] Example 10
[668] Tables XVIII and XIX below show the characterization of the variants of the two subfamily members.
[669]
[670]
[671] Table XX below provides the results of the fluorescence serum bactericidal assay for 2086 subfamily A.
[672]
[673] Example 11
[674] The following description further demonstrates that P2086 is expressed in Neisseria strains, and provides additional embodiments for P2086 expression in some strains.
[675] Cell lysis was prepared using cells from plate culture and resuspended in SDS sample buffer and then heated at 98 ° C. for 4 minutes. Samples were loaded in 10-20% pre-cast gels (ICN) at a total protein amount of about 30-50 μg per well and run at 175V. The gel was transferred to nitrocellulose membrane and then blocked for 30 minutes with 5% milk powder (Blotto) in Tris-buffered saline. The primary antibody used was a collection of polyclonal antiserum generated against individual rLP2086 variants in mice.
[676] Referring to Figures 17 and 18, Western blots show the reactivity of rLP2086 mouse antiserum against P2086 subfamily A and B whole cell lysis. For subfamily A cell fusion blots, the antiserum used was generated for rLP2086-2996, -870446 and -250771, of which rLP2086-250771 was diluted 1/500 in bloto and the rest in bloto Diluted to 1/1000. For subfamily B cell fusion blots, the antiserum used was rLP2086-8529 (diluted 1/1000 in bloto), -CDC1573, -M982 and -880049 (three diluted 1/500 in bloto) It was created. Primary antiserum and blots were incubated overnight at 4 ° C. The blot was washed, goat-anti-mouse AP secondary antibody was added diluted 1/500 in the blotto, and the blot was incubated for 30 min at room temperature. After washing, blots were developed using BCIP / NBT membrane phosphatase substrate system (KPL).
[677] List of References
[678] The above-referenced references herein are described below, which are incorporated herein by reference in their entirety.
[679]
[680]
[681]
[682]
[683]
[684]
[685]
[686]
[687]
[688]
[689]
[690] It will now be appreciated by those skilled in the art that the present invention has been fully described, and that numerous changes and modifications can be made to this application without departing from the spirit or scope of the invention described herein. The above describes preferred embodiments of the invention with a number of possible variations. However, these embodiments are illustrative only and the present invention is not limited thereto.
SEQUENCE LISTING <110> Zlotnick, Gary      Fletcher, Leah      John, Farley      Bernfield, Liesel      Zagursky, Robert      Metcalf, Benjamin <120> Novel Immunogenic Compositions for the Prevention and Treatment of Meningococcal Disease <130> 38523.000016 <150> US 60 / 328,101 <151> 2001-10-11 <150> US 60 / 406,934 <151> 2002-08-30 <160> 329 <170> PatentIn version 3.1 <210> 1 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 1tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accacaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacggaca aaccatcacg ctggcaagcg gcgaatttca aatatacaaa 300cagaaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 420ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgac 480ccgaacggca ggctgcacta ctccattgat tttaccaaaa aacagggtta cggcagaatc 540gaacacctga aaacgcccga gcagaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 2 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 2Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Thr Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Thr Ile Thr Leu Ala Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asn His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln Gly                165 170 175Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 3 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 3tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccacac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacgg acaaaccatc acgctggcaa gcggcgaatt tcaaatatac 300aaacagaacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggcgg agaacatacc 420gccttcaacc aactgcctga cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gacccgaacg gcaggctgca ctactccatt gattttacca aaaaacaggg ttacggcaga 540atcgaacacc tgaaaacgcc cgagcagaat gtcgagcttg cctccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcggcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720aagataaggg aaaaggttca cgaaatcggc atcgccggca aacagtag 768 <210> 4 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 4Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Thr Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Thr Ile Thr Leu Ala Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asn His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln                165 170 175Gly Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Lys Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 5 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 5atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accacaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacggaca aaccatcacg ctggcaagcg gcgaatttca aatatacaaa 300cagaaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 420ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgac 480ccgaacggca ggctgcacta ctccattgat tttaccaaaa aacagggtta cggcagaatc 540gaacacctga aaacgcccga gcagaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 6 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 6Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Thr Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Thr Ile Thr Leu Ala Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asn His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln Gly                165 170 175Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 7 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 7tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accacaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacggaca aaccatcacg ctggcaagcg gcgaatttca aatatacaaa 300cagaaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 420ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgac 480ccgaacggca ggctgcacta ctccattgat tttaccaaaa aacagggtta cggcagaatc 540gaacacctga aaacgcccga gcagaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggcccggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccagcaaac agtag 765 <210> 8 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 8Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Thr Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Thr Ile Thr Leu Ala Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asn His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln Gly                165 170 175Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Pro Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Ser Lys Gln                245 250 <210> 9 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 9tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccacac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacgg acaaaccatc acgctggcaa gcggcgaatt tcaaatatac 300aaacagaacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggcgg agaacatacc 420gccttcaacc aactgcctga cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gacccgaacg gcaggctgca ctactccatt gattttacca aaaaacaggg ttacggcaga 540atcgaacacc tgaaaacgcc cgagcagaat gtcgagcttg cctccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcggcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggccc ggcaaccgtg 720aagataaggg aaaaggttca cgaaatcggc atcgccagca aacagtag 768 <210> 10 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 10Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Thr Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Thr Ile Thr Leu Ala Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asn His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln                165 170 175Gly Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Pro Ala Thr Val225 230 235 240Lys Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Ser Lys Gln                245 250 255 <210> 11 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 11atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accacaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacggaca aaccatcacg ctggcaagcg gcgaatttca aatatacaaa 300cagaaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 420ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgac 480ccgaacggca ggctgcacta ctccattgat tttaccaaaa aacagggtta cggcagaatc 540gaacacctga aaacgcccga gcagaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggcccggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccagcaaac agtag 765 <210> 12 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 12Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Thr Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Thr Ile Thr Leu Ala Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asn His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln Gly                165 170 175Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Pro Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Ser Lys Gln                245 250 <210> 13 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 13tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcggag tggacggaca aaccatcacg ctggcaagcg gcgaatttca aatatacaaa 300cagaaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 420ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgac 480ccgaacggca ggctgcacta ctccattgat tttaccaaaa aacagggtta cggcagaatc 540gaacacctga aaacgcccga gcagaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 14 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 14Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Gly Val Asp Gly Gln Thr Ile Thr Leu Ala Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asn His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln Gly                165 170 175Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 15 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 15tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg gagtggacgg acaaaccatc acgctggcaa gcggcgaatt tcaaatatac 300aaacagaacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggcgg agaacatacc 420gccttcaacc aactgcctga cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gacccgaacg gcaggctgca ctactccatt gattttacca aaaaacaggg ttacggcaga 540atcgaacacc tgaaaacgcc cgagcagaat gtcgagcttg cctccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcggcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720aagataaggg aaaaggttca cgaaatcggc atcgccggca aacagtag 768 <210> 16 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 16Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Gly Val Asp Gly Gln Thr Ile Thr Leu Ala Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asn His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln                165 170 175Gly Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Lys Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 17 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 17atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcggag tggacggaca aaccatcacg ctggcaagcg gcgaatttca aatatacaaa 300cagaaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 420ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgac 480ccgaacggca ggctgcacta ctccattgat tttaccaaaa aacagggtta cggcagaatc 540gaacacctga aaacgcccga gcagaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 18 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 18Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Gly Val Asp Gly Gln Thr Ile Thr Leu Ala Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asn His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln Gly                165 170 175Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 19 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 19tgcagcagca gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacggaca aaccatcacg ctggcaagcg gcgaatttca aatatacaaa 300cagaaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 420ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgac 480ccgaacggca ggctgcacta ctccattgat tttaccaaaa aacagggtta cggcagaatc 540gaacacctga aaacgcccga gcagaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 20 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 20Cys Ser Ser Arg Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Thr Ile Thr Leu Ala Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asn His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln Gly                165 170 175Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 21 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 21tgcggatcca gcagaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacgg acaaaccatc acgctggcaa gcggcgaatt tcaaatatac 300aaacagaacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggcgg agaacatacc 420gccttcaacc aactgcctga cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gacccgaacg gcaggctgca ctactccatt gattttacca aaaaacaggg ttacggcaga 540atcgaacacc tgaaaacgcc cgagcagaat gtcgagcttg cctccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcggcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720aagataaggg aaaaggttca cgaaatcggc atcgccggca aacagtag 768 <210> 22 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 22Cys Gly Ser Ser Arg Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Thr Ile Thr Leu Ala Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asn His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln                165 170 175Gly Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Lys Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 23 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 23atgagcagca gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacggaca aaccatcacg ctggcaagcg gcgaatttca aatatacaaa 300cagaaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 420ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgac 480ccgaacggca ggctgcacta ctccattgat tttaccaaaa aacagggtta cggcagaatc 540gaacacctga aaacgcccga gcagaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 24 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 24Met Ser Ser Arg Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Thr Ile Thr Leu Ala Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asn His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln Gly                165 170 175Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 25 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 25tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgt tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgac 480ccgaacggca ggctgcacta ctccattgat tttaccaaaa aacagggtta cggcagaatc 540gaacacctga aaacgcccga gcagaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 26 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 26Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Phe Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln Gly                165 170 175Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 27 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 27tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgttcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaaatatac 300aaacaggacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggtgg agaacatacc 420gccttcaacc aactgcccag cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gacccgaacg gcaggctgca ctactccatt gattttacca aaaaacaggg ttacggcaga 540atcgaacacc tgaaaacgcc cgagcagaat gtcgagcttg cctccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcggcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720aagataaggg aaaaggttca cgaaatcggc atcgccggca aacagtag 768 <210> 28 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 28Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Phe Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln                165 170 175Gly Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Lys Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 29 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 29atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgt tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgac 480ccgaacggca ggctgcacta ctccattgat tttaccaaaa aacagggtta cggcagaatc 540gaacacctga aaacgcccga gcagaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 30 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 30Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Phe Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln Gly                165 170 175Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 31 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 31tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgac 480ccgaacggca ggctgcacta ctccattgat tttaccaaaa aacagggtta cggcagaatc 540gaacacctga aaacgcccga gcagaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 32 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 32Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln Gly                165 170 175Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 33 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 33tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaaatatac 300aaacaggacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggtgg agaacatacc 420gccttcaacc aactgcccag cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gacccgaacg gcaggctgca ctactccatt gattttacca aaaaacaggg ttacggcaga 540atcgaacacc tgaaaacgcc cgagcagaat gtcgagcttg cctccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcggcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720aagataaggg aaaaggttca cgaaatcggc atcgccggca aacagtag 768 <210> 34 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 34Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln                165 170 175Gly Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Lys Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 35 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 35atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgac 480ccgaacggca ggctgcacta ctccattgat tttaccaaaa aacagggtta cggcagaatc 540gaacacctga aaacgcccga gcagaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 36 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 36Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln Gly                165 170 175Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 37 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 37tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgac 480ccgaacggca ggctgcacta ctccattgat tttaccaaaa aacagggtta cggcagaatc 540gaacacctga aaacgcccga gcagaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 38 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 38Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln Gly                165 170 175Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 39 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 39tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaaatatac 300aaacaggacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggtgg agaacatacc 420gccttcaacc aactgcccag cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gacccgaacg gcaggctgca ctactccatt gattttacca aaaaacaggg ttacggcaga 540atcgaacacc tgaaaacgcc cgagcagaat gtcgagcttg cctccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcggcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720aagataaggg aaaaggttca cgaaatcggc atcgccggca aacagtag 768 <210> 40 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 40Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln                165 170 175Gly Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Lys Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 41 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 41atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgac 480ccgaacggca ggctgcacta ctccattgat tttaccaaaa aacagggtta cggcagaatc 540gaacacctga aaacgcccga gcagaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 42 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 42Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln Gly                165 170 175Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 43 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 43tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgac 480ccgaacggca ggctgcacta ctccattgat tttaccaaaa aacagggtta cggcagaatc 540gaacacctga aaacgcccga gcagaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 44 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 44Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln Gly                165 170 175Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 45 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 45tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaaatatac 300aaacaggacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggtgg agaacatacc 420gccttcaacc aactgcccag cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gacccgaacg gcaggctgca ctactccatt gattttacca aaaaacaggg ttacggcaga 540atcgaacacc tgaaaacgcc cgagcagaat gtcgagcttg cctccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcggcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720aagataaggg aaaaggttca cgaaatcggc atcgccggca aacagtag 768 <210> 46 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 46Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln                165 170 175Gly Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Lys Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 47 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 47atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgac 480ccgaacggca ggctgcacta ctccattgat tttaccaaaa aacagggtta cggcagaatc 540gaacacctga aaacgcccga gcagaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 48 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 48Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Pro Asn Gly Arg Leu His Tyr Ser Ile Asp Phe Thr Lys Lys Gln Gly                165 170 175Tyr Gly Arg Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 49 <211> 786 <212> DNA <213> Neisseria meningitidis <400> 49tgcagcagcg gaagcggaag cggaggcggc ggtgtcgccg ccgacatcgg cacagggctt 60gccgatgcac taactgcgcc gctcgaccat aaagacaaag gtttgaaatc cctgacattg 120gaagactcca tttcccaaaa cggaacactg accctgtcgg cacaaggtgc ggaaaaaact 180ttcaaagtcg gcgacaaaga caacagtctc aatacaggca aattgaagaa cgacaaaatc 240agccgcttcg actttgtgca aaaaatcgaa gtggacggac aaaccatcac gctggcaagc 300ggcgaatttc aaatatacaa acaggaccac tccgccgtcg ttgccctaca gattgaaaaa 360atcaacaacc ccgacaaaat cgacagcctg ataaaccaac gctccttcct tgtcagcggt 420ttgggcggag aacataccgc cttcaaccaa ctgcccagcg gcaaagccga gtatcacggc 480aaagcattca gctccgacga tgccggcgga aaactgacct ataccataga ttttgccgcc 540aaacagggac acggcaaaat cgaacacctg aaaacacccg agcagaatgt cgagcttgcc 600tccgccgaac tcaaagcaga tgaaaaatca cacgccgtca ttttgggcga cacgcgctac 660ggcagcgaag aaaaaggcac ttaccacctc gctcttttcg gcgaccgagc ccaagaaatc 720gccggctcgg caaccgtgaa gataagggaa aaggttcacg aaatcggcat cgccggcaaa 780cagtag 786 <210> 50 <211> 261 <212> PRT <213> Neisseria meningitidis <400> 50Cys Ser Ser Gly Ser Gly Ser Gly Gly Gly Gly Val Ala Ala Asp Ile1 5 10 15Gly Thr Gly Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp            20 25 30Lys Gly Leu Lys Ser Leu Thr Leu Glu Asp Ser Ile Ser Gln Asn Gly        35 40 45Thr Leu Thr Leu Ser Ala Gln Gly Ala Glu Lys Thr Phe Lys Val Gly    50 55 60Asp Lys Asp Asn Ser Leu Asn Thr Gly Lys Leu Lys Asn Asp Lys Ile65 70 75 80Ser Arg Phe Asp Phe Val Gln Lys Ile Glu Val Asp Gly Gln Thr Ile                85 90 95Thr Leu Ala Ser Gly Glu Phe Gln Ile Tyr Lys Gln Asp His Ser Ala            100 105 110Val Val Ala Leu Gln Ile Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp        115 120 125Ser Leu Ile Asn Gln Arg Ser Phe Leu Val Ser Gly Leu Gly Gly Glu    130 135 140His Thr Ala Phe Asn Gln Leu Pro Ser Gly Lys Ala Glu Tyr His Gly145 150 155 160Lys Ala Phe Ser Ser Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile                165 170 175Asp Phe Ala Ala Lys Gln Gly His Gly Lys Ile Glu His Leu Lys Thr            180 185 190Pro Glu Gln Asn Val Glu Leu Ala Ser Ala Glu Leu Lys Ala Asp Glu        195 200 205Lys Ser His Ala Val Ile Leu Gly Asp Thr Arg Tyr Gly Ser Glu Glu    210 215 220Lys Gly Thr Tyr His Leu Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile225 230 235 240Ala Gly Ser Ala Thr Val Lys Ile Arg Glu Lys Val His Glu Ile Gly                245 250 255Ile Ala Gly Lys Gln            260 <210> 51 <211> 789 <212> DNA <213> Neisseria meningitidis <400> 51tgcggatcca gcggaagcgg aagcggaggc ggcggtgtcg ccgccgacat cggcacaggg 60cttgccgatg cactaactgc gccgctcgac cataaagaca aaggtttgaa atccctgaca 120ttggaagact ccatttccca aaacggaaca ctgaccctgt cggcacaagg tgcggaaaaa 180actttcaaag tcggcgacaa agacaacagt ctcaatacag gcaaattgaa gaacgacaaa 240atcagccgct tcgactttgt gcaaaaaatc gaagtggacg gacaaaccat cacgctggca 300agcggcgaat ttcaaatata caaacaggac cactccgccg tcgttgccct acagattgaa 360aaaatcaaca accccgacaa aatcgacagc ctgataaacc aacgctcctt ccttgtcagc 420ggtttgggcg gagaacatac cgccttcaac caactgccca gcggcaaagc cgagtatcac 480ggcaaagcat tcagctccga cgatgccggc ggaaaactga cctataccat agattttgcc 540gccaaacagg gacacggcaa aatcgaacac ctgaaaacac ccgagcagaa tgtcgagctt 600gcctccgccg aactcaaagc agatgaaaaa tcacacgccg tcattttggg cgacacgcgc 660tacggcagcg aagaaaaagg cacttaccac ctcgctcttt tcggcgaccg agcccaagaa 720atcgccggct cggcaaccgt gaagataagg gaaaaggttc acgaaatcgg catcgccggc 780aaacagtag 789 <210> 52 <211> 262 <212> PRT <213> Neisseria meningitidis <400> 52Cys Gly Ser Ser Gly Ser Gly Ser Gly Gly Gly Gly Val Ala Ala Asp1 5 10 15Ile Gly Thr Gly Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys            20 25 30Asp Lys Gly Leu Lys Ser Leu Thr Leu Glu Asp Ser Ile Ser Gln Asn        35 40 45Gly Thr Leu Thr Leu Ser Ala Gln Gly Ala Glu Lys Thr Phe Lys Val    50 55 60Gly Asp Lys Asp Asn Ser Leu Asn Thr Gly Lys Leu Lys Asn Asp Lys65 70 75 80Ile Ser Arg Phe Asp Phe Val Gln Lys Ile Glu Val Asp Gly Gln Thr                85 90 95Ile Thr Leu Ala Ser Gly Glu Phe Gln Ile Tyr Lys Gln Asp His Ser            100 105 110Ala Val Val Ala Leu Gln Ile Glu Lys Ile Asn Asn Pro Asp Lys Ile        115 120 125Asp Ser Leu Ile Asn Gln Arg Ser Phe Leu Val Ser Gly Leu Gly Gly    130 135 140Glu His Thr Ala Phe Asn Gln Leu Pro Ser Gly Lys Ala Glu Tyr His145 150 155 160Gly Lys Ala Phe Ser Ser Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr                165 170 175Ile Asp Phe Ala Ala Lys Gln Gly His Gly Lys Ile Glu His Leu Lys            180 185 190Thr Pro Glu Gln Asn Val Glu Leu Ala Ser Ala Glu Leu Lys Ala Asp        195 200 205Glu Lys Ser His Ala Val Ile Leu Gly Asp Thr Arg Tyr Gly Ser Glu    210 215 220Glu Lys Gly Thr Tyr His Leu Ala Leu Phe Gly Asp Arg Ala Gln Glu225 230 235 240Ile Ala Gly Ser Ala Thr Val Lys Ile Arg Glu Lys Val His Glu Ile                245 250 255Gly Ile Ala Gly Lys Gln            260 <210> 53 <211> 786 <212> DNA <213> Neisseria meningitidis <400> 53atgagcagcg gaagcggaag cggaggcggc ggtgtcgccg ccgacatcgg cacagggctt 60gccgatgcac taactgcgcc gctcgaccat aaagacaaag gtttgaaatc cctgacattg 120gaagactcca tttcccaaaa cggaacactg accctgtcgg cacaaggtgc ggaaaaaact 180ttcaaagtcg gcgacaaaga caacagtctc aatacaggca aattgaagaa cgacaaaatc 240agccgcttcg actttgtgca aaaaatcgaa gtggacggac aaaccatcac gctggcaagc 300ggcgaatttc aaatatacaa acaggaccac tccgccgtcg ttgccctaca gattgaaaaa 360atcaacaacc ccgacaaaat cgacagcctg ataaaccaac gctccttcct tgtcagcggt 420ttgggcggag aacataccgc cttcaaccaa ctgcccagcg gcaaagccga gtatcacggc 480aaagcattca gctccgacga tgccggcgga aaactgacct ataccataga ttttgccgcc 540aaacagggac acggcaaaat cgaacacctg aaaacacccg agcagaatgt cgagcttgcc 600tccgccgaac tcaaagcaga tgaaaaatca cacgccgtca ttttgggcga cacgcgctac 660ggcagcgaag aaaaaggcac ttaccacctc gctcttttcg gcgaccgagc ccaagaaatc 720gccggctcgg caaccgtgaa gataagggaa aaggttcacg aaatcggcat cgccggcaaa 780cagtag 786 <210> 54 <211> 261 <212> PRT <213> Neisseria meningitidis <400> 54Met Ser Ser Gly Ser Gly Ser Gly Gly Gly Gly Val Ala Ala Asp Ile1 5 10 15Gly Thr Gly Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp            20 25 30Lys Gly Leu Lys Ser Leu Thr Leu Glu Asp Ser Ile Ser Gln Asn Gly        35 40 45Thr Leu Thr Leu Ser Ala Gln Gly Ala Glu Lys Thr Phe Lys Val Gly    50 55 60Asp Lys Asp Asn Ser Leu Asn Thr Gly Lys Leu Lys Asn Asp Lys Ile65 70 75 80Ser Arg Phe Asp Phe Val Gln Lys Ile Glu Val Asp Gly Gln Thr Ile                85 90 95Thr Leu Ala Ser Gly Glu Phe Gln Ile Tyr Lys Gln Asp His Ser Ala            100 105 110Val Val Ala Leu Gln Ile Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp        115 120 125Ser Leu Ile Asn Gln Arg Ser Phe Leu Val Ser Gly Leu Gly Gly Glu    130 135 140His Thr Ala Phe Asn Gln Leu Pro Ser Gly Lys Ala Glu Tyr His Gly145 150 155 160Lys Ala Phe Ser Ser Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile                165 170 175Asp Phe Ala Ala Lys Gln Gly His Gly Lys Ile Glu His Leu Lys Thr            180 185 190Pro Glu Gln Asn Val Glu Leu Ala Ser Ala Glu Leu Lys Ala Asp Glu        195 200 205Lys Ser His Ala Val Ile Leu Gly Asp Thr Arg Tyr Gly Ser Glu Glu    210 215 220Lys Gly Thr Tyr His Leu Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile225 230 235 240Ala Gly Ser Ala Thr Val Lys Ile Arg Glu Lys Val His Glu Ile Gly                245 250 255Ile Ala Gly Lys Gln            260 <210> 55 <211> 786 <212> DNA <213> Neisseria meningitidis <400> 55tgcagcagcg gaagcggaag cggaggcggc ggtgtcgccg ccgacatcgg cacagggctt 60gccgatgcac taactgcgcc gctcgaccat aaagacaaag gtttgaaatc cctgacattg 120gaagactcca tttcccaaaa cggaacactg accctgtcgg cacaaggtgc ggaaaaaact 180ttcaaagtcg gcgacaaaga caacagtctc aatacaggca aattgaagaa cgacaaaatc 240agccgcttcg actttgtgca aaaaatcgaa gtggacggac aaaccatcac gctggcaagc 300ggcgaatttc aaatatacaa acaggaccac tccgccgtcg ttgccctaca gattgaaaaa 360atcaacaacc ccgacaaaat cgacagcctg ataaaccaac gctccttcct tgtcagcggt 420ttgggcggag aacataccgc cttcaaccaa ctgcccagcg gcaaagccga gtatcacggc 480aaagcattca gctccgacga tgccggcgga aaactgacct ataccataga ttttgccgcc 540aaacagggac acggcaaaat cgaacacctg aaaacacccg agcagaatgt cgagcttgcc 600tccgccgaac tcaaagcaga tgaaaaatca cacgccgtca ttttgggcga cacgcgctac 660ggcagcgaag aaaaaggcac ttaccacctc gctcttttcg gcgaccgagc ccaagaaatc 720gccggctcgg caaccgtgaa gataagggaa aaggttcacg aaatcggcat cgccggcaaa 780cagtag 786 <210> 56 <211> 261 <212> PRT <213> Neisseria meningitidis <400> 56Cys Ser Ser Gly Ser Gly Ser Gly Gly Gly Gly Val Ala Ala Asp Ile1 5 10 15Gly Thr Gly Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp            20 25 30Lys Gly Leu Lys Ser Leu Thr Leu Glu Asp Ser Ile Ser Gln Asn Gly        35 40 45Thr Leu Thr Leu Ser Ala Gln Gly Ala Glu Lys Thr Phe Lys Val Gly    50 55 60Asp Lys Asp Asn Ser Leu Asn Thr Gly Lys Leu Lys Asn Asp Lys Ile65 70 75 80Ser Arg Phe Asp Phe Val Gln Lys Ile Glu Val Asp Gly Gln Thr Ile                85 90 95Thr Leu Ala Ser Gly Glu Phe Gln Ile Tyr Lys Gln Asp His Ser Ala            100 105 110Val Val Ala Leu Gln Ile Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp        115 120 125Ser Leu Ile Asn Gln Arg Ser Phe Leu Val Ser Gly Leu Gly Gly Glu    130 135 140His Thr Ala Phe Asn Gln Leu Pro Ser Gly Lys Ala Glu Tyr His Gly145 150 155 160Lys Ala Phe Ser Ser Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile                165 170 175Asp Phe Ala Ala Lys Gln Gly His Gly Lys Ile Glu His Leu Lys Thr            180 185 190Pro Glu Gln Asn Val Glu Leu Ala Ser Ala Glu Leu Lys Ala Asp Glu        195 200 205Lys Ser His Ala Val Ile Leu Gly Asp Thr Arg Tyr Gly Ser Glu Glu    210 215 220Lys Gly Thr Tyr His Leu Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile225 230 235 240Ala Gly Ser Ala Thr Val Lys Ile Arg Glu Lys Val His Glu Ile Gly                245 250 255Ile Ala Gly Lys Gln            260 <210> 57 <211> 789 <212> DNA <213> Neisseria meningitidis <400> 57tgcggatcca gcggaagcgg aagcggaggc ggcggtgtcg ccgccgacat cggcacaggg 60cttgccgatg cactaactgc gccgctcgac cataaagaca aaggtttgaa atccctgaca 120ttggaagact ccatttccca aaacggaaca ctgaccctgt cggcacaagg tgcggaaaaa 180actttcaaag tcggcgacaa agacaacagt ctcaatacag gcaaattgaa gaacgacaaa 240atcagccgct tcgactttgt gcaaaaaatc gaagtggacg gacaaaccat cacgctggca 300agcggcgaat ttcaaatata caaacaggac cactccgccg tcgttgccct acagattgaa 360aaaatcaaca accccgacaa aatcgacagc ctgataaacc aacgctcctt ccttgtcagc 420ggtttgggcg gagaacatac cgccttcaac caactgccca gcggcaaagc cgagtatcac 480ggcaaagcat tcagctccga cgatgccggc ggaaaactga cctataccat agattttgcc 540gccaaacagg gacacggcaa aatcgaacac ctgaaaacac ccgagcagaa tgtcgagctt 600gcctccgccg aactcaaagc agatgaaaaa tcacacgccg tcattttggg cgacacgcgc 660tacggcagcg aagaaaaagg cacttaccac ctcgctcttt tcggcgaccg agcccaagaa 720atcgccggct cggcaaccgt gaagataagg gaaaaggttc acgaaatcgg catcgccggc 780aaacagtag 789 <210> 58 <211> 262 <212> PRT <213> Neisseria meningitidis <400> 58Cys Gly Ser Ser Gly Ser Gly Ser Gly Gly Gly Gly Val Ala Ala Asp1 5 10 15Ile Gly Thr Gly Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys            20 25 30Asp Lys Gly Leu Lys Ser Leu Thr Leu Glu Asp Ser Ile Ser Gln Asn        35 40 45Gly Thr Leu Thr Leu Ser Ala Gln Gly Ala Glu Lys Thr Phe Lys Val    50 55 60Gly Asp Lys Asp Asn Ser Leu Asn Thr Gly Lys Leu Lys Asn Asp Lys65 70 75 80Ile Ser Arg Phe Asp Phe Val Gln Lys Ile Glu Val Asp Gly Gln Thr                85 90 95Ile Thr Leu Ala Ser Gly Glu Phe Gln Ile Tyr Lys Gln Asp His Ser            100 105 110Ala Val Val Ala Leu Gln Ile Glu Lys Ile Asn Asn Pro Asp Lys Ile        115 120 125Asp Ser Leu Ile Asn Gln Arg Ser Phe Leu Val Ser Gly Leu Gly Gly    130 135 140Glu His Thr Ala Phe Asn Gln Leu Pro Ser Gly Lys Ala Glu Tyr His145 150 155 160Gly Lys Ala Phe Ser Ser Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr                165 170 175Ile Asp Phe Ala Ala Lys Gln Gly His Gly Lys Ile Glu His Leu Lys            180 185 190Thr Pro Glu Gln Asn Val Glu Leu Ala Ser Ala Glu Leu Lys Ala Asp        195 200 205Glu Lys Ser His Ala Val Ile Leu Gly Asp Thr Arg Tyr Gly Ser Glu    210 215 220Glu Lys Gly Thr Tyr His Leu Ala Leu Phe Gly Asp Arg Ala Gln Glu225 230 235 240Ile Ala Gly Ser Ala Thr Val Lys Ile Arg Glu Lys Val His Glu Ile                245 250 255Gly Ile Ala Gly Lys Gln            260 <210> 59 <211> 786 <212> DNA <213> Neisseria meningitidis <400> 59atgagcagcg gaagcggaag cggaggcggc ggtgtcgccg ccgacatcgg cacagggctt 60gccgatgcac taactgcgcc gctcgaccat aaagacaaag gtttgaaatc cctgacattg 120gaagactcca tttcccaaaa cggaacactg accctgtcgg cacaaggtgc ggaaaaaact 180ttcaaagtcg gcgacaaaga caacagtctc aatacaggca aattgaagaa cgacaaaatc 240agccgcttcg actttgtgca aaaaatcgaa gtggacggac aaaccatcac gctggcaagc 300ggcgaatttc aaatatacaa acaggaccac tccgccgtcg ttgccctaca gattgaaaaa 360atcaacaacc ccgacaaaat cgacagcctg ataaaccaac gctccttcct tgtcagcggt 420ttgggcggag aacataccgc cttcaaccaa ctgcccagcg gcaaagccga gtatcacggc 480aaagcattca gctccgacga tgccggcgga aaactgacct ataccataga ttttgccgcc 540aaacagggac acggcaaaat cgaacacctg aaaacacccg agcagaatgt cgagcttgcc 600tccgccgaac tcaaagcaga tgaaaaatca cacgccgtca ttttgggcga cacgcgctac 660ggcagcgaag aaaaaggcac ttaccacctc gctcttttcg gcgaccgagc ccaagaaatc 720gccggctcgg caaccgtgaa gataagggaa aaggttcacg aaatcggcat cgccggcaaa 780cagtag 786 <210> 60 <211> 261 <212> PRT <213> Neisseria meningitidis <400> 60Met Ser Ser Gly Ser Gly Ser Gly Gly Gly Gly Val Ala Ala Asp Ile1 5 10 15Gly Thr Gly Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp            20 25 30Lys Gly Leu Lys Ser Leu Thr Leu Glu Asp Ser Ile Ser Gln Asn Gly        35 40 45Thr Leu Thr Leu Ser Ala Gln Gly Ala Glu Lys Thr Phe Lys Val Gly    50 55 60Asp Lys Asp Asn Ser Leu Asn Thr Gly Lys Leu Lys Asn Asp Lys Ile65 70 75 80Ser Arg Phe Asp Phe Val Gln Lys Ile Glu Val Asp Gly Gln Thr Ile                85 90 95Thr Leu Ala Ser Gly Glu Phe Gln Ile Tyr Lys Gln Asp His Ser Ala            100 105 110Val Val Ala Leu Gln Ile Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp        115 120 125Ser Leu Ile Asn Gln Arg Ser Phe Leu Val Ser Gly Leu Gly Gly Glu    130 135 140His Thr Ala Phe Asn Gln Leu Pro Ser Gly Lys Ala Glu Tyr His Gly145 150 155 160Lys Ala Phe Ser Ser Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile                165 170 175Asp Phe Ala Ala Lys Gln Gly His Gly Lys Ile Glu His Leu Lys Thr            180 185 190Pro Glu Gln Asn Val Glu Leu Ala Ser Ala Glu Leu Lys Ala Asp Glu        195 200 205Lys Ser His Ala Val Ile Leu Gly Asp Thr Arg Tyr Gly Ser Glu Glu    210 215 220Lys Gly Thr Tyr His Leu Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile225 230 235 240Ala Gly Ser Ala Thr Val Lys Ile Arg Glu Lys Val His Glu Ile Gly                245 250 255Ile Ala Gly Lys Gln            260 <210> 61 <211> 789 <212> DNA <213> Neisseria meningitidis <400> 61tgcagcagcg gaggcggcgg aagcggaggc ggcggtgtcg ccgccgacat cggcacgggg 60cttgccgatg cactaactgc gccgctcgac cataaagaca aaggtttgaa atccctgaca 120ttggaagact ctattcccca aaacggaaca ctaaccctgt cggcacaagg tgcggaaaaa 180actttcaaag ccggcgacaa agacaacagc ctcaacacgg gcaaactgaa gaacgacaaa 240atcagccgct tcgactttgt gcaaaaaatc gaagtggacg gacaaaccat cacgctggca 300agcggcgaat ttcaaatata caaacaggac cactccgccg tcgttgccct acagattgaa 360aaaatcaaca accccgacaa aatcgacagc ctgataaacc aacgctcctt ccttgtcagc 420ggtttgggcg gagaacatac cgccttcaac caactgcccg gcggcaaagc cgagtatcac 480ggcaaagcat tcagctccga cgacccgaac ggcaggctgc actactccat tgattttacc 540aaaaaacagg gttacggcgg aatcgaacac ctgaaaacac ccgagcaaaa tgtcgagctt 600gcctccgccg aactcaaagc agatgaaaaa tcacacgccg tcattttggg cgacacgcgc 660tacggcagcg aagaaaaagg cacttaccac ctcgcccttt tcggcgaccg cgcccaagaa 720atcgccggct cggcaaccgt gaagataggg gaaaaggttc acgaaatcgg catcgccggc 780aaacagtag 789 <210> 62 <211> 262 <212> PRT <213> Neisseria meningitidis <400> 62Cys Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Val Ala Ala Asp1 5 10 15Ile Gly Thr Gly Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys            20 25 30Asp Lys Gly Leu Lys Ser Leu Thr Leu Glu Asp Ser Ile Pro Gln Asn        35 40 45Gly Thr Leu Thr Leu Ser Ala Gln Gly Ala Glu Lys Thr Phe Lys Ala    50 55 60Gly Asp Lys Asp Asn Ser Leu Asn Thr Gly Lys Leu Lys Asn Asp Lys65 70 75 80Ile Ser Arg Phe Asp Phe Val Gln Lys Ile Glu Val Asp Gly Gln Thr                85 90 95Ile Thr Leu Ala Ser Gly Glu Phe Gln Ile Tyr Lys Gln Asp His Ser            100 105 110Ala Val Val Ala Leu Gln Ile Glu Lys Ile Asn Asn Pro Asp Lys Ile        115 120 125Asp Ser Leu Ile Asn Gln Arg Ser Phe Leu Val Ser Gly Leu Gly Gly    130 135 140Glu His Thr Ala Phe Asn Gln Leu Pro Gly Gly Lys Ala Glu Tyr His145 150 155 160Gly Lys Ala Phe Ser Ser Asp Asp Pro Asn Gly Arg Leu His Tyr Ser                165 170 175Ile Asp Phe Thr Lys Lys Gln Gly Tyr Gly Gly Ile Glu His Leu Lys            180 185 190Thr Pro Glu Gln Asn Val Glu Leu Ala Ser Ala Glu Leu Lys Ala Asp        195 200 205Glu Lys Ser His Ala Val Ile Leu Gly Asp Thr Arg Tyr Gly Ser Glu    210 215 220Glu Lys Gly Thr Tyr His Leu Ala Leu Phe Gly Asp Arg Ala Gln Glu225 230 235 240Ile Ala Gly Ser Ala Thr Val Lys Ile Gly Glu Lys Val His Glu Ile                245 250 255Gly Ile Ala Gly Lys Gln            260 <210> 63 <211> 792 <212> DNA <213> Neisseria meningitidis <400> 63tgcggatcca gcggaggcgg cggaagcgga ggcggcggtg tcgccgccga catcggcacg 60gggcttgccg atgcactaac tgcgccgctc gaccataaag acaaaggttt gaaatccctg 120acattggaag actctattcc ccaaaacgga acactaaccc tgtcggcaca aggtgcggaa 180aaaactttca aagccggcga caaagacaac agcctcaaca cgggcaaact gaagaacgac 240aaaatcagcc gcttcgactt tgtgcaaaaa atcgaagtgg acggacaaac catcacgctg 300gcaagcggcg aatttcaaat atacaaacag gaccactccg ccgtcgttgc cctacagatt 360gaaaaaatca acaaccccga caaaatcgac agcctgataa accaacgctc cttccttgtc 420agcggtttgg gcggagaaca taccgccttc aaccaactgc ccggcggcaa agccgagtat 480cacggcaaag cattcagctc cgacgacccg aacggcaggc tgcactactc cattgatttt 540accaaaaaac agggttacgg cggaatcgaa cacctgaaaa cacccgagca aaatgtcgag 600cttgcctccg ccgaactcaa agcagatgaa aaatcacacg ccgtcatttt gggcgacacg 660cgctacggca gcgaagaaaa aggcacttac cacctcgccc ttttcggcga ccgcgcccaa 720gaaatcgccg gctcggcaac cgtgaagata ggggaaaagg ttcacgaaat cggcatcgcc 780ggcaaacagt ag 792 <210> 64 <211> 263 <212> PRT <213> Neisseria meningitidis <400> 64Cys Gly Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Val Ala Ala1 5 10 15Asp Ile Gly Thr Gly Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His            20 25 30Lys Asp Lys Gly Leu Lys Ser Leu Thr Leu Glu Asp Ser Ile Pro Gln        35 40 45Asn Gly Thr Leu Thr Leu Ser Ala Gln Gly Ala Glu Lys Thr Phe Lys    50 55 60Ala Gly Asp Lys Asp Asn Ser Leu Asn Thr Gly Lys Leu Lys Asn Asp65 70 75 80Lys Ile Ser Arg Phe Asp Phe Val Gln Lys Ile Glu Val Asp Gly Gln                85 90 95Thr Ile Thr Leu Ala Ser Gly Glu Phe Gln Ile Tyr Lys Gln Asp His            100 105 110Ser Ala Val Val Ala Leu Gln Ile Glu Lys Ile Asn Asn Pro Asp Lys        115 120 125Ile Asp Ser Leu Ile Asn Gln Arg Ser Phe Leu Val Ser Gly Leu Gly    130 135 140Gly Glu His Thr Ala Phe Asn Gln Leu Pro Gly Gly Lys Ala Glu Tyr145 150 155 160His Gly Lys Ala Phe Ser Ser Asp Asp Pro Asn Gly Arg Leu His Tyr                165 170 175Ser Ile Asp Phe Thr Lys Lys Gln Gly Tyr Gly Gly Ile Glu His Leu            180 185 190Lys Thr Pro Glu Gln Asn Val Glu Leu Ala Ser Ala Glu Leu Lys Ala        195 200 205Asp Glu Lys Ser His Ala Val Ile Leu Gly Asp Thr Arg Tyr Gly Ser    210 215 220Glu Glu Lys Gly Thr Tyr His Leu Ala Leu Phe Gly Asp Arg Ala Gln225 230 235 240Glu Ile Ala Gly Ser Ala Thr Val Lys Ile Gly Glu Lys Val His Glu                245 250 255Ile Gly Ile Ala Gly Lys Gln            260 <210> 65 <211> 789 <212> DNA <213> Neisseria meningitidis <400> 65atgagcagcg gaggcggcgg aagcggaggc ggcggtgtcg ccgccgacat cggcacgggg 60cttgccgatg cactaactgc gccgctcgac cataaagaca aaggtttgaa atccctgaca 120ttggaagact ctattcccca aaacggaaca ctaaccctgt cggcacaagg tgcggaaaaa 180actttcaaag ccggcgacaa agacaacagc ctcaacacgg gcaaactgaa gaacgacaaa 240atcagccgct tcgactttgt gcaaaaaatc gaagtggacg gacaaaccat cacgctggca 300agcggcgaat ttcaaatata caaacaggac cactccgccg tcgttgccct acagattgaa 360aaaatcaaca accccgacaa aatcgacagc ctgataaacc aacgctcctt ccttgtcagc 420ggtttgggcg gagaacatac cgccttcaac caactgcccg gcggcaaagc cgagtatcac 480ggcaaagcat tcagctccga cgacccgaac ggcaggctgc actactccat tgattttacc 540aaaaaacagg gttacggcgg aatcgaacac ctgaaaacac ccgagcaaaa tgtcgagctt 600gcctccgccg aactcaaagc agatgaaaaa tcacacgccg tcattttggg cgacacgcgc 660tacggcagcg aagaaaaagg cacttaccac ctcgcccttt tcggcgaccg cgcccaagaa 720atcgccggct cggcaaccgt gaagataggg gaaaaggttc acgaaatcgg catcgccggc 780aaacagtag 789 <210> 66 <211> 262 <212> PRT <213> Neisseria meningitidis <400> 66Met Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Val Ala Ala Asp1 5 10 15Ile Gly Thr Gly Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys            20 25 30Asp Lys Gly Leu Lys Ser Leu Thr Leu Glu Asp Ser Ile Pro Gln Asn        35 40 45Gly Thr Leu Thr Leu Ser Ala Gln Gly Ala Glu Lys Thr Phe Lys Ala    50 55 60Gly Asp Lys Asp Asn Ser Leu Asn Thr Gly Lys Leu Lys Asn Asp Lys65 70 75 80Ile Ser Arg Phe Asp Phe Val Gln Lys Ile Glu Val Asp Gly Gln Thr                85 90 95Ile Thr Leu Ala Ser Gly Glu Phe Gln Ile Tyr Lys Gln Asp His Ser            100 105 110Ala Val Val Ala Leu Gln Ile Glu Lys Ile Asn Asn Pro Asp Lys Ile        115 120 125Asp Ser Leu Ile Asn Gln Arg Ser Phe Leu Val Ser Gly Leu Gly Gly    130 135 140Glu His Thr Ala Phe Asn Gln Leu Pro Gly Gly Lys Ala Glu Tyr His145 150 155 160Gly Lys Ala Phe Ser Ser Asp Asp Pro Asn Gly Arg Leu His Tyr Ser                165 170 175Ile Asp Phe Thr Lys Lys Gln Gly Tyr Gly Gly Ile Glu His Leu Lys            180 185 190Thr Pro Glu Gln Asn Val Glu Leu Ala Ser Ala Glu Leu Lys Ala Asp        195 200 205Glu Lys Ser His Ala Val Ile Leu Gly Asp Thr Arg Tyr Gly Ser Glu    210 215 220Glu Lys Gly Thr Tyr His Leu Ala Leu Phe Gly Asp Arg Ala Gln Glu225 230 235 240Ile Ala Gly Ser Ala Thr Val Lys Ile Gly Glu Lys Val His Glu Ile                245 250 255Gly Ile Ala Gly Lys Gln            260 <210> 67 <211> 774 <212> DNA <213> Neisseria meningitidis <400> 67tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaggt ttgaaatccc tgacattgga agactccatt 120tcccaaaacg gaacactgac cctgtcggca caaggtgcgg aaaaaacttt caaagtcggc 180gacaaagaca acagtctcaa tacaggcaaa ttgaagaacg acaaaatcag ccgcttcgac 240tttgtgcaaa aaatcgaagt ggacggacaa accatcacgc tggcaagcgg cgaatttcaa 300atatacaaac agaaccactc cgccgtcgtt gccctacaga ttgaaaaaat caacaacccc 360gacaaaatcg acagcctgat aaaccaacgc tccttccttg tcagcggttt gggcggagaa 420cataccgcct tcaaccaact gcccggcggc aaagccgagt atcacggcaa agcattcagc 480tccgacgatg ccggcggaaa actgacctat accatagatt ttgccgccaa acagggacac 540ggcaaaatcg aacacctgaa aacacccgag caaaatgtcg agcttgccgc cgccgaactc 600aaagcagatg aaaaatcaca cgccgtcatt ttgggcgaca cgcgctacgg cagcgaagaa 660aaaggcactt accacctcgc ccttttcggc gaccgcgctc aagaaatcgc cggctcggca 720accgtgaaga taggagaaaa ggttcacgaa atcagcatcg ccggcaaaca gtag 774 <210> 68 <211> 257 <212> PRT <213> Neisseria meningitidis <400> 68Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu Lys            20 25 30Ser Leu Thr Leu Glu Asp Ser Ile Ser Gln Asn Gly Thr Leu Thr Leu        35 40 45Ser Ala Gln Gly Ala Glu Lys Thr Phe Lys Val Gly Asp Lys Asp Asn    50 55 60Ser Leu Asn Thr Gly Lys Leu Lys Asn Asp Lys Ile Ser Arg Phe Asp65 70 75 80Phe Val Gln Lys Ile Glu Val Asp Gly Gln Thr Ile Thr Leu Ala Ser                85 90 95Gly Glu Phe Gln Ile Tyr Lys Gln Asn His Ser Ala Val Val Ala Leu            100 105 110Gln Ile Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn        115 120 125Gln Arg Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe    130 135 140Asn Gln Leu Pro Gly Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser145 150 155 160Ser Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala                165 170 175Lys Gln Gly His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn            180 185 190Val Glu Leu Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala        195 200 205Val Ile Leu Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr    210 215 220His Leu Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala225 230 235 240Thr Val Lys Ile Gly Glu Lys Val His Glu Ile Ser Ile Ala Gly Lys                245 250 255Gln     <210> 69 <211> 777 <212> DNA <213> Neisseria meningitidis <400> 69tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa ggtttgaaat ccctgacatt ggaagactcc 120atttcccaaa acggaacact gaccctgtcg gcacaaggtg cggaaaaaac tttcaaagtc 180ggcgacaaag acaacagtct caatacaggc aaattgaaga acgacaaaat cagccgcttc 240gactttgtgc aaaaaatcga agtggacgga caaaccatca cgctggcaag cggcgaattt 300caaatataca aacagaacca ctccgccgtc gttgccctac agattgaaaa aatcaacaac 360cccgacaaaa tcgacagcct gataaaccaa cgctccttcc ttgtcagcgg tttgggcgga 420gaacataccg ccttcaacca actgcccggc ggcaaagccg agtatcacgg caaagcattc 480agctccgacg atgccggcgg aaaactgacc tataccatag attttgccgc caaacaggga 540cacggcaaaa tcgaacacct gaaaacaccc gagcaaaatg tcgagcttgc cgccgccgaa 600ctcaaagcag atgaaaaatc acacgccgtc attttgggcg acacgcgcta cggcagcgaa 660gaaaaaggca cttaccacct cgcccttttc ggcgaccgcg ctcaagaaat cgccggctcg 720gcaaccgtga agataggaga aaaggttcac gaaatcagca tcgccggcaa acagtag 777 <210> 70 <211> 258 <212> PRT <213> Neisseria meningitidis <400> 70Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu            20 25 30Lys Ser Leu Thr Leu Glu Asp Ser Ile Ser Gln Asn Gly Thr Leu Thr        35 40 45Leu Ser Ala Gln Gly Ala Glu Lys Thr Phe Lys Val Gly Asp Lys Asp    50 55 60Asn Ser Leu Asn Thr Gly Lys Leu Lys Asn Asp Lys Ile Ser Arg Phe65 70 75 80Asp Phe Val Gln Lys Ile Glu Val Asp Gly Gln Thr Ile Thr Leu Ala                85 90 95Ser Gly Glu Phe Gln Ile Tyr Lys Gln Asn His Ser Ala Val Val Ala            100 105 110Leu Gln Ile Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile        115 120 125Asn Gln Arg Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala    130 135 140Phe Asn Gln Leu Pro Gly Gly Lys Ala Glu Tyr His Gly Lys Ala Phe145 150 155 160Ser Ser Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala                165 170 175Ala Lys Gln Gly His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln            180 185 190Asn Val Glu Leu Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His        195 200 205Ala Val Ile Leu Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr    210 215 220Tyr His Leu Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser225 230 235 240Ala Thr Val Lys Ile Gly Glu Lys Val His Glu Ile Ser Ile Ala Gly                245 250 255Lys gln         <210> 71 <211> 774 <212> DNA <213> Neisseria meningitidis <400> 71atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaggt ttgaaatccc tgacattgga agactccatt 120tcccaaaacg gaacactgac cctgtcggca caaggtgcgg aaaaaacttt caaagtcggc 180gacaaagaca acagtctcaa tacaggcaaa ttgaagaacg acaaaatcag ccgcttcgac 240tttgtgcaaa aaatcgaagt ggacggacaa accatcacgc tggcaagcgg cgaatttcaa 300atatacaaac agaaccactc cgccgtcgtt gccctacaga ttgaaaaaat caacaacccc 360gacaaaatcg acagcctgat aaaccaacgc tccttccttg tcagcggttt gggcggagaa 420cataccgcct tcaaccaact gcccggcggc aaagccgagt atcacggcaa agcattcagc 480tccgacgatg ccggcggaaa actgacctat accatagatt ttgccgccaa acagggacac 540ggcaaaatcg aacacctgaa aacacccgag caaaatgtcg agcttgccgc cgccgaactc 600aaagcagatg aaaaatcaca cgccgtcatt ttgggcgaca cgcgctacgg cagcgaagaa 660aaaggcactt accacctcgc ccttttcggc gaccgcgctc aagaaatcgc cggctcggca 720accgtgaaga taggagaaaa ggttcacgaa atcagcatcg ccggcaaaca gtag 774 <210> 72 <211> 257 <212> PRT <213> Neisseria meningitidis <400> 72Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu Lys            20 25 30Ser Leu Thr Leu Glu Asp Ser Ile Ser Gln Asn Gly Thr Leu Thr Leu        35 40 45Ser Ala Gln Gly Ala Glu Lys Thr Phe Lys Val Gly Asp Lys Asp Asn    50 55 60Ser Leu Asn Thr Gly Lys Leu Lys Asn Asp Lys Ile Ser Arg Phe Asp65 70 75 80Phe Val Gln Lys Ile Glu Val Asp Gly Gln Thr Ile Thr Leu Ala Ser                85 90 95Gly Glu Phe Gln Ile Tyr Lys Gln Asn His Ser Ala Val Val Ala Leu            100 105 110Gln Ile Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn        115 120 125Gln Arg Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe    130 135 140Asn Gln Leu Pro Gly Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser145 150 155 160Ser Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala                165 170 175Lys Gln Gly His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn            180 185 190Val Glu Leu Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala        195 200 205Val Ile Leu Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr    210 215 220His Leu Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala225 230 235 240Thr Val Lys Ile Gly Glu Lys Val His Glu Ile Ser Ile Ala Gly Lys                245 250 255Gln     <210> 73 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 73tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacttga aaacacccga gcaaaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttctcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatt gccggcaaac agtag 765 <210> 74 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 74Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Leu Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 75 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 75tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaaatatac 300aaacaggacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggtgg agaacatacc 420gccttcaacc aactgcccag cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gatgctggcg gaaaactgac ctataccata gatttcgccg ccaaacaggg acacggcaaa 540atcgaacact tgaaaacacc cgagcaaaat gtcgagcttg cctccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcggcga agaaaaaggc 660acttaccacc tcgcccttct cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720aagataaggg aaaaggttca cgaaatcggc attgccggca aacagtag 768 <210> 76 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 76Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Leu Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Lys Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 77 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 77atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacttga aaacacccga gcaaaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttctcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatt gccggcaaac agtag 765 <210> 78 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 78Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Leu Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 79 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 79tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacttga aaacacccga gcaaaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 80 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 80Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 81 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 81tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaaatatac 300aaacaggacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggtgg agaacatacc 420gccttcaacc aactgcccag cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gatgctggcg gaaaactgac ctataccata gatttcgccg ccaaacaggg acacggcaaa 540atcgaacact tgaaaacacc cgagcaaaat gtcgagcttg cctccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcggcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720aagataaggg aaaaggttca cgaaatcggc atcgccggca aacagtag 768 <210> 82 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 82Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Lys Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 83 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 83atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacttga aaacacccga gcaaaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 84 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 84Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 85 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 85tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacttga aaacacccga gcaaaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 86 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 86Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 87 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 87tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaaatatac 300aaacaggacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggtgg agaacatacc 420gccttcaacc aactgcccag cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gatgctggcg gaaaactgac ctataccata gatttcgccg ccaaacaggg acacggcaaa 540atcgaacact tgaaaacacc cgagcaaaat gtcgagcttg cctccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcggcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720aagataaggg aaaaggttca cgaaatcggc atcgccggca aacagtag 768 <210> 88 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 88Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Lys Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 89 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 89atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacttga aaacacccga gcaaaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 90 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 90Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 91 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 91tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacttga aaacacccga gcaaaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 92 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 92Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 93 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 93tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaaatatac 300aaacaggacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggtgg agaacatacc 420gccttcaacc aactgcccag cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gatgctggcg gaaaactgac ctataccata gatttcgccg ccaaacaggg acacggcaaa 540atcgaacact tgaaaacacc cgagcaaaat gtcgagcttg cctccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcggcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720aagataaggg aaaaggttca cgaaatcggc atcgccggca aacagtag 768 <210> 94 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 94Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Lys Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 95 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 95atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacttga aaacacccga gcaaaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 96 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 96Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 97 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 97tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacttga aaacacccga gcaaaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtaa 765 <210> 98 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 98Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 99 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 99tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaaatatac 300aaacaggacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggtgg agaacatacc 420gccttcaacc aactgcccag cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gatgctggcg gaaaactgac ctataccata gatttcgccg ccaaacaggg acacggcaaa 540atcgaacact tgaaaacacc cgagcaaaat gtcgagcttg cctccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcggcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720aagataaggg aaaaggttca cgaaatcggc atcgccggca aacagtaa 768 <210> 100 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 100Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Lys Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 101 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 101atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacttga aaacacccga gcaaaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtaa 765 <210> 102 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 102Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 103 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 103tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctta atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacttga aaacacccga gcaaaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 104 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 104Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 105 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 105tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc ttaatacggg caaattgaag aacgacaagg tcagccgttt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaaatatac 300aaacaggacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggtgg agaacatacc 420gccttcaacc aactgcccag cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gatgctggcg gaaaactgac ctataccata gatttcgccg ccaaacaggg acacggcaaa 540atcgaacact tgaaaacacc cgagcaaaat gtcgagcttg cctccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcggcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720aagataaggg aaaaggttca cgaaatcggc atcgccggca aacagtag 768 <210> 106 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 106Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Lys Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 107 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 107atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctta atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacttga aaacacccga gcaaaatgtc gagcttgcct ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcggcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataagggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 108 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 108Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ser Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Gly Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Arg Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 109 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 109tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg agaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 420ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacctga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataggggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 110 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 110Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 111 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 111tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggagaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaaatatac 300aaacaggacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggcgg agaacatacc 420gccttcaacc aactgcctga cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gatgctggcg gaaaactgac ctataccata gatttcgccg ccaaacaggg acacggcaaa 540atcgaacacc tgaaaacacc cgagcaaaat gtcgagcttg ccgccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcagcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720aagatagggg aaaaggttca cgaaatcggc atcgccggca aacagtag 768 <210> 112 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 112Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Lys Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 113 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 113atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg agaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 420ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacctga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataggggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 114 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 114Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 115 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 115tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 420ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacctga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataggggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 116 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 116Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 117 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 117tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaaatatac 300aaacaggacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggcgg agaacatacc 420gccttcaacc aactgcctga cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gatgctggcg gaaaactgac ctataccata gatttcgccg ccaaacaggg acacggcaaa 540atcgaacacc tgaaaacacc cgagcaaaat gtcgagcttg ccgccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcagcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720aagatagggg aaaaggttca cgaaatcggc atcgccggca aacagtag 768 <210> 118 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 118Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Lys Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 119 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 119atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 420ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacctga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataggggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 120 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 120Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 121 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 121tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 420ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacctga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataggggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 122 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 122Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 123 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 123tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaaatatac 300aaacaggacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggcgg agaacatacc 420gccttcaacc aactgcctga cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gatgctggcg gaaaactgac ctataccata gatttcgccg ccaaacaggg acacggcaaa 540atcgaacacc tgaaaacacc cgagcaaaat gtcgagcttg ccgccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcagcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720aagatagggg aaaaggttca cgaaatcggc atcgccggca aacagtag 768 <210> 124 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 124Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Lys Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 125 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 125atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 420ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacctga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataggggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 126 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 126Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 127 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 127tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 420ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacctga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataggggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 128 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 128Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 129 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 129tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaaatatac 300aaacaggacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggcgg agaacatacc 420gccttcaacc aactgcctga cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gatgctggcg gaaaactgac ctataccata gatttcgccg ccaaacaggg acacggcaaa 540atcgaacacc tgaaaacacc cgagcaaaat gtcgagcttg ccgccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcagcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720aagatagggg aaaaggttca cgaaatcggc atcgccggca aacagtag 768 <210> 130 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 130Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Lys Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 131 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 131atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 420ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacctga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataggggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 132 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 132Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 133 <211> 765 <212> DNA <213> Neisseria meningitidis <133> 133tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 420ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacctga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataggggaaa aggttcacga aatcggcatc gccggcaaac agtaa 765 <210> 134 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 134Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 135 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 135tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaaatatac 300aaacaggacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggcgg agaacatacc 420gccttcaacc aactgcctga cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gatgctggcg gaaaactgac ctataccata gatttcgccg ccaaacaggg acacggcaaa 540atcgaacacc tgaaaacacc cgagcaaaat gtcgagcttg ccgccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcagcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720aagatagggg aaaaggttca cgaaatcggc atcgccggca aacagtaa 768 <210> 136 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 136Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Lys Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 137 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 137atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 420ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacctga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataggggaaa aggttcacga aatcggcatc gccggcaaac agtaa 765 <210> 138 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 138Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <139> <211> 765 <212> DNA <213> Neisseria meningitidis <400> 139tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctta atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccacca aacagggaca cggcaaaatc 540gaacacttga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataggggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 140 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 140Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Thr Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 141 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 141tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc ttaatacggg caaattgaag aacgacaagg tcagccgttt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaaatatac 300aaacaggacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggtgg agaacatacc 420gccttcaacc aactgcccag cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gatgctggcg gaaaactgac ctataccata gatttcgcca ccaaacaggg acacggcaaa 540atcgaacact tgaaaacacc cgagcaaaat gtcgagcttg ccgccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcagcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720aagatagggg aaaaggttca cgaaatcggc atcgccggca aacagtag 768 <210> 142 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 142Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Thr Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Lys Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 143 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 143atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctta atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccacca aacagggaca cggcaaaatc 540gaacacttga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataggggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 144 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 144Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Thr Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 145 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 145tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctta atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccacca aacagggaca cggcaaaatc 540gaacacttga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataggggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 146 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 146Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Thr Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 147 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 147tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc ttaatacggg caaattgaag aacgacaagg tcagccgttt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaaatatac 300aaacaggacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggtgg agaacatacc 420gccttcaacc aactgcccag cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gatgctggcg gaaaactgac ctataccata gatttcgcca ccaaacaggg acacggcaaa 540atcgaacact tgaaaacacc cgagcaaaat gtcgagcttg ccgccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcagcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720aagatagggg aaaaggttca cgaaatcggc atcgccggca aacagtag 768 <210> 148 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 148Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Thr Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Lys Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 149 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 149atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctta atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccacca aacagggaca cggcaaaatc 540gaacacttga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataggggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 150 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 150Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Thr Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 151 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 151tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctta atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccacca aacagggaca cggcaaaatc 540gaacacttga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataggggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 152 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 152Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Thr Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 153 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 153tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc ttaatacggg caaattgaag aacgacaagg tcagccgttt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaaatatac 300aaacaggacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggtgg agaacatacc 420gccttcaacc aactgcccag cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gatgctggcg gaaaactgac ctataccata gatttcgcca ccaaacaggg acacggcaaa 540atcgaacact tgaaaacacc cgagcaaaat gtcgagcttg ccgccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcagcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720aagatagggg aaaaggttca cgaaatcggc atcgccggca aacagtag 768 <210> 154 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 154Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Thr Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Lys Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 155 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 155atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctta atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccagcgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccacca aacagggaca cggcaaaatc 540gaacacttga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataggggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 156 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 156Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Ser Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Thr Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 157 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 157tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgactataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctatag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccggcgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacctga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgct caagaaatcg ccggctcggc aaccgtgaag 720ataggggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 158 <211> 253 <212> PRT <213> Neisseria meningitidis <400> 158Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp Tyr Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Ile Glu Lys            100 105 110Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser Phe        115 120 125Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu Pro    130 135 140Gly Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp Ala145 150 155 160Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly His                165 170 175Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu Ala            180 185 190Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu Gly        195 200 205Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala Leu    210 215 220Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys Ile225 230 235 240Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 159 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 159tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacta taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaaatatac 300aaacaggacc actccgccgt cgttgcccta tagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggtgg agaacatacc 420gccttcaacc aactgcccgg cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gatgctggcg gaaaactgac ctataccata gatttcgccg ccaaacaggg acacggcaaa 540atcgaacacc tgaaaacacc cgagcaaaat gtcgagcttg ccgccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcagcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gctcaagaaa tcgccggctc ggcaaccgtg 720aagatagggg aaaaggttca cgaaatcggc atcgccggca aacagtag 768 <210> 160 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 160Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp Tyr Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Gly Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 161 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 161atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgactataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctatag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggtggaga acataccgcc 420ttcaaccaac tgcccggcgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacctga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgct caagaaatcg ccggctcggc aaccgtgaag 720ataggggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 162 <211> 253 <212> PRT <213> Neisseria meningitidis <400> 162Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp Tyr Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Ile Glu Lys            100 105 110Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser Phe        115 120 125Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu Pro    130 135 140Gly Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp Ala145 150 155 160Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly His                165 170 175Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu Ala            180 185 190Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu Gly        195 200 205Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala Leu    210 215 220Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys Ile225 230 235 240Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 163 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 163tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccgacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 420ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacctga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataggggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 164 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 164Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Arg Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 165 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 165tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaaatatac 300aaacaggacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaaccg acgctccttc cttgtcagcg gtttgggcgg agaacatacc 420gccttcaacc aactgcctga cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gatgctggcg gaaaactgac ctataccata gatttcgccg ccaaacaggg acacggcaaa 540atcgaacacc tgaaaacacc cgagcaaaat gtcgagcttg ccgccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcagcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720aagatagggg aaaaggttca cgaaatcggc atcgccggca aacagtag 768 <210> 166 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 166Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Arg Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Lys Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 167 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 167atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccgacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 420ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacctga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 720ataggggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 168 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 168Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Arg Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Lys225 230 235 240Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 169 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 169tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 420ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacctga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtggag 720ataggggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 170 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 170Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Glu225 230 235 240Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <210> 171 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 171tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaaatatac 300aaacaggacc actccgccgt cgttgcccta cagattgaaa aaatcaacaa ccccgacaaa 360atcgacagcc tgataaacca acgctccttc cttgtcagcg gtttgggcgg agaacatacc 420gccttcaacc aactgcctga cggcaaagcc gagtatcacg gcaaagcatt cagctccgac 480gatgctggcg gaaaactgac ctataccata gatttcgccg ccaaacaggg acacggcaaa 540atcgaacacc tgaaaacacc cgagcaaaat gtcgagcttg ccgccgccga actcaaagca 600gatgaaaaat cacacgccgt cattttgggc gacacgcgct acggcagcga agaaaaaggc 660acttaccacc tcgccctttt cggcgaccgc gcccaagaaa tcgccggctc ggcaaccgtg 720gagatagggg aaaaggttca cgaaatcggc atcgccggca aacagtag 768 <210> 172 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 172Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile            100 105 110Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg        115 120 125Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln    130 135 140Leu Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu            180 185 190Leu Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile        195 200 205Leu Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu    210 215 220Ala Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val225 230 235 240Glu Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 255 <210> 173 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 173atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca aatatacaaa 300caggaccact ccgccgtcgt tgccctacag attgaaaaaa tcaacaaccc cgacaaaatc 360gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 420ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgat 480gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 540gaacacctga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 600gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 660taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtggag 720ataggggaaa aggttcacga aatcggcatc gccggcaaac agtag 765 <210> 174 <211> 254 <212> PRT <213> Neisseria meningitidis <400> 174Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Asp His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Asp Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly                165 170 175His Gly Lys Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Ala Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Ser Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Phe Gly Asp Arg Ala Gln Glu Ile Ala Gly Ser Ala Thr Val Glu225 230 235 240Ile Gly Glu Lys Val His Glu Ile Gly Ile Ala Gly Lys Gln                245 250 <175> 175 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 175tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggtgcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca agtgtacaaa 300caaagccatt ccgccttaac cgcccttcag accgagcaag tacaagattc ggagcattca 360gggaagatgg ttgcgaaacg ccagttcaga atcggcgata tagcgggtga acatacatct 420tttgacaagc ttcccgaagg cggcagggcg acatatcgcg ggacggcatt cggttcagac 480gatgccagtg gaaaactgac ctacaccata gatttcgccg ccaagcaggg acacggcaaa 540atcgaacatt tgaaatcgcc agaactcaat gttgacctgg ccgcctccga tatcaagccg 600gataaaaaac gccatgccgt catcagcggt tccgtccttt acaaccaagc cgagaaaggc 660agttactctc taggcatctt tggcgggcaa gcccaggaag ttgccggcag cgcagaagtg 720gaaaccgcaa acggcatacg ccatatcggt cttgccgcca agcagtaa 768 <210> 176 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 176Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Val Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Leu Gln Thr Glu            100 105 110Gln Val Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg Gln        115 120 125Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Ser Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Asp            180 185 190Leu Ala Ala Ser Asp Ile Lys Pro Asp Lys Lys Arg His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Gln Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Glu Thr Ala Asn Gly Ile Arg His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 177 <211> 771 <212> DNA <213> Neisseria meningitidis <400> 177tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggtgct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaagtgtac 300aaacaaagcc attccgcctt aaccgccctt cagaccgagc aagtacaaga ttcggagcat 360tcagggaaga tggttgcgaa acgccagttc agaatcggcg atatagcggg tgaacataca 420tcttttgaca agcttcccga aggcggcagg gcgacatatc gcgggacggc attcggttca 480gacgatgcca gtggaaaact gacctacacc atagatttcg ccgccaagca gggacacggc 540aaaatcgaac atttgaaatc gccagaactc aatgttgacc tggccgcctc cgatatcaag 600ccggataaaa aacgccatgc cgtcatcagc ggttccgtcc tttacaacca agccgagaaa 660ggcagttact ctctaggcat ctttggcggg caagcccagg aagttgccgg cagcgcagaa 720gtggaaaccg caaacggcat acgccatatc ggtcttgccg ccaagcagta a 771 <210> 178 <211> 256 <212> PRT <213> Neisseria meningitidis <400> 178Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Val1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Leu Gln Thr            100 105 110Glu Gln Val Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg        115 120 125Gln Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys    130 135 140Leu Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser145 150 155 160Asp Asp Ala Ser Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys                165 170 175Gln Gly His Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val            180 185 190Asp Leu Ala Ala Ser Asp Ile Lys Pro Asp Lys Lys Arg His Ala Val        195 200 205Ile Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser    210 215 220Leu Gly Ile Phe Gly Gly Gln Ala Gln Glu Val Ala Gly Ser Ala Glu225 230 235 240Val Glu Thr Ala Asn Gly Ile Arg His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 179 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 179atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggtgcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca agtgtacaaa 300caaagccatt ccgccttaac cgcccttcag accgagcaag tacaagattc ggagcattca 360gggaagatgg ttgcgaaacg ccagttcaga atcggcgata tagcgggtga acatacatct 420tttgacaagc ttcccgaagg cggcagggcg acatatcgcg ggacggcatt cggttcagac 480gatgccagtg gaaaactgac ctacaccata gatttcgccg ccaagcaggg acacggcaaa 540atcgaacatt tgaaatcgcc agaactcaat gttgacctgg ccgcctccga tatcaagccg 600gataaaaaac gccatgccgt catcagcggt tccgtccttt acaaccaagc cgagaaaggc 660agttactctc taggcatctt tggcgggcaa gcccaggaag ttgccggcag cgcagaagtg 720gaaaccgcaa acggcatacg ccatatcggt cttgccgcca agcagtaa 768 <210> 180 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 180Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Val Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Leu Gln Thr Glu            100 105 110Gln Val Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg Gln        115 120 125Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Ser Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Asp            180 185 190Leu Ala Ala Ser Asp Ile Lys Pro Asp Lys Lys Arg His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Gln Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Glu Thr Ala Asn Gly Ile Arg His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 181 <211> 747 <212> DNA <213> Neisseria meningitidis <400> 181tgcagcagcg gagggggtgg tgtcgccgcc gacatcggtg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaggt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggt 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgc 240caaatcgaag tggacgggca gctcattacc ttggagagtg gagagttcca agtatacaaa 300caaagccatt ccgccttaac cgcctttcag accgagcaaa tacaagattc ggagcattcc 360gggaagatgg ttgcgaaacg ccagttcaga atcggcgaca tagcgggcga acatacatct 420tttgacaagc ttcccgaagg cggcagggcg acatatcgcg ggacggcgtt cggttcagac 480gatgccggcg gaaaactgac ctacaccata gatttcgccg ccaagcaggg aaacggcaaa 540atcgaacatt tgaaatcgcc agaactcaat gtcgacctgg ccgccgccga tatcaagccg 600gatggaaaac gccatgccgt catcagcggt tccgtccttt acaaccaagc cgagaaaggc 660agttactccc tcggtatctt tggcggaaaa gcccaggaag ttgccggcag cgcggaagtg 720aaaaccgtaa acggcatacg ccatatc 747 <210> 182 <211> 249 <212> PRT <213> Neisseria meningitidis <400> 182Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Phe Gln Thr Glu            100 105 110Gln Ile Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg Gln        115 120 125Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly Asn Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Asp            180 185 190Leu Ala Ala Ala Asp Ile Lys Pro Asp Gly Lys Arg His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Lys Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Lys Thr Val Asn Gly Ile Arg His Ile                245 <210> 183 <211> 750 <212> DNA <213> Neisseria meningitidis <400> 183tgcggatcca gcggaggggg tggtgtcgcc gccgacatcg gtgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa ggtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggtgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgttt cgactttatc 240cgccaaatcg aagtggacgg gcagctcatt accttggaga gtggagagtt ccaagtatac 300aaacaaagcc attccgcctt aaccgccttt cagaccgagc aaatacaaga ttcggagcat 360tccgggaaga tggttgcgaa acgccagttc agaatcggcg acatagcggg cgaacataca 420tcttttgaca agcttcccga aggcggcagg gcgacatatc gcgggacggc gttcggttca 480gacgatgccg gcggaaaact gacctacacc atagatttcg ccgccaagca gggaaacggc 540aaaatcgaac atttgaaatc gccagaactc aatgtcgacc tggccgccgc cgatatcaag 600ccggatggaa aacgccatgc cgtcatcagc ggttccgtcc tttacaacca agccgagaaa 660ggcagttact ccctcggtat ctttggcgga aaagcccagg aagttgccgg cagcgcggaa 720gtgaaaaccg taaacggcat acgccatatc 750 <210> 184 <211> 250 <212> PRT <213> Neisseria meningitidis <400> 184Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Phe Gln Thr            100 105 110Glu Gln Ile Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg        115 120 125Gln Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys    130 135 140Leu Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser145 150 155 160Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys                165 170 175Gln Gly Asn Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val            180 185 190Asp Leu Ala Ala Ala Asp Ile Lys Pro Asp Gly Lys Arg His Ala Val        195 200 205Ile Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser    210 215 220Leu Gly Ile Phe Gly Gly Lys Ala Gln Glu Val Ala Gly Ser Ala Glu225 230 235 240Val Lys Thr Val Asn Gly Ile Arg His Ile                245 250 <210> 185 <211> 747 <212> DNA <213> Neisseria meningitidis <400> 185atgagcagcg gagggggtgg tgtcgccgcc gacatcggtg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaggt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggt 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgc 240caaatcgaag tggacgggca gctcattacc ttggagagtg gagagttcca agtatacaaa 300caaagccatt ccgccttaac cgcctttcag accgagcaaa tacaagattc ggagcattcc 360gggaagatgg ttgcgaaacg ccagttcaga atcggcgaca tagcgggcga acatacatct 420tttgacaagc ttcccgaagg cggcagggcg acatatcgcg ggacggcgtt cggttcagac 480gatgccggcg gaaaactgac ctacaccata gatttcgccg ccaagcaggg aaacggcaaa 540atcgaacatt tgaaatcgcc agaactcaat gtcgacctgg ccgccgccga tatcaagccg 600gatggaaaac gccatgccgt catcagcggt tccgtccttt acaaccaagc cgagaaaggc 660agttactccc tcggtatctt tggcggaaaa gcccaggaag ttgccggcag cgcggaagtg 720aaaaccgtaa acggcatacg ccatatc 747 <210> 186 <211> 249 <212> PRT <213> Neisseria meningitidis <400> 186Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Phe Gln Thr Glu            100 105 110Gln Ile Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg Gln        115 120 125Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly Asn Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Asp            180 185 190Leu Ala Ala Ala Asp Ile Lys Pro Asp Gly Lys Arg His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Lys Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Lys Thr Val Asn Gly Ile Arg His Ile                245 <210> 187 <211> 747 <212> DNA <213> Neisseria meningitidis <400> 187tgcagcagcg gagggggtgg tgtcgccgcc gacatcggtg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaggt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggt 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgc 240caaatcgaag tggacgggca gctcattacc ttggagagtg gagagttcca agtatacaaa 300caaagccatt ccgccttaac cgcctttcag accgagcaaa tacaagattc ggagcattcc 360gggaagatgg ttgcgaaacg ccagttcaga atcggcgaca tagcgggcga acatacatct 420tttgacaagc ttcccgaagg cggcagggcg acatatcgcg ggacggcgtt cggttcagac 480gatgccggcg gaaaactgac ctacaccata gatttcgccg ccaagcaggg aaacggcaaa 540atcgaacatt tgaaatcgcc agaactcaat gtcgacctgg ccgccgccga tatcaagccg 600gatggaaaac gccatgccgt catcagcggt tccgtccttt acaaccaagc cgagaaaggc 660agttactccc tcggtatctt tggcggaaaa gcccaggaag ttgccggcag cgcggaagtg 720aaaaccgtaa acggcatacg ccatatc 747 <210> 188 <211> 249 <212> PRT <213> Neisseria meningitidis <400> 188Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Phe Gln Thr Glu            100 105 110Gln Ile Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg Gln        115 120 125Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly Asn Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Asp            180 185 190Leu Ala Ala Ala Asp Ile Lys Pro Asp Gly Lys Arg His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Lys Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Lys Thr Val Asn Gly Ile Arg His Ile                245 <210> 189 <211> 750 <212> DNA <213> Neisseria meningitidis <400> 189tgcggatcca gcggaggggg tggtgtcgcc gccgacatcg gtgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa ggtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggtgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgttt cgactttatc 240cgccaaatcg aagtggacgg gcagctcatt accttggaga gtggagagtt ccaagtatac 300aaacaaagcc attccgcctt aaccgccttt cagaccgagc aaatacaaga ttcggagcat 360tccgggaaga tggttgcgaa acgccagttc agaatcggcg acatagcggg cgaacataca 420tcttttgaca agcttcccga aggcggcagg gcgacatatc gcgggacggc gttcggttca 480gacgatgccg gcggaaaact gacctacacc atagatttcg ccgccaagca gggaaacggc 540aaaatcgaac atttgaaatc gccagaactc aatgtcgacc tggccgccgc cgatatcaag 600ccggatggaa aacgccatgc cgtcatcagc ggttccgtcc tttacaacca agccgagaaa 660ggcagttact ccctcggtat ctttggcgga aaagcccagg aagttgccgg cagcgcggaa 720gtgaaaaccg taaacggcat acgccatatc 750 <210> 190 <211> 250 <212> PRT <213> Neisseria meningitidis <400> 190Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Phe Gln Thr            100 105 110Glu Gln Ile Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg        115 120 125Gln Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys    130 135 140Leu Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser145 150 155 160Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys                165 170 175Gln Gly Asn Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val            180 185 190Asp Leu Ala Ala Ala Asp Ile Lys Pro Asp Gly Lys Arg His Ala Val        195 200 205Ile Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser    210 215 220Leu Gly Ile Phe Gly Gly Lys Ala Gln Glu Val Ala Gly Ser Ala Glu225 230 235 240Val Lys Thr Val Asn Gly Ile Arg His Ile                245 250 <210> 191 <211> 747 <212> DNA <213> Neisseria meningitidis <400> 191atgagcagcg gagggggtgg tgtcgccgcc gacatcggtg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaggt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggt 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgc 240caaatcgaag tggacgggca gctcattacc ttggagagtg gagagttcca agtatacaaa 300caaagccatt ccgccttaac cgcctttcag accgagcaaa tacaagattc ggagcattcc 360gggaagatgg ttgcgaaacg ccagttcaga atcggcgaca tagcgggcga acatacatct 420tttgacaagc ttcccgaagg cggcagggcg acatatcgcg ggacggcgtt cggttcagac 480gatgccggcg gaaaactgac ctacaccata gatttcgccg ccaagcaggg aaacggcaaa 540atcgaacatt tgaaatcgcc agaactcaat gtcgacctgg ccgccgccga tatcaagccg 600gatggaaaac gccatgccgt catcagcggt tccgtccttt acaaccaagc cgagaaaggc 660agttactccc tcggtatctt tggcggaaaa gcccaggaag ttgccggcag cgcggaagtg 720aaaaccgtaa acggcatacg ccatatc 747 <210> 192 <211> 249 <212> PRT <213> Neisseria meningitidis <400> 192Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Phe Gln Thr Glu            100 105 110Gln Ile Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg Gln        115 120 125Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly Asn Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Asp            180 185 190Leu Ala Ala Ala Asp Ile Lys Pro Asp Gly Lys Arg His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Lys Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Lys Thr Val Asn Gly Ile Arg His Ile                245 <210> 193 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 193tgcagcagcg gagggggtgg tgtcgccgcc gacatcggtg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaggt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggt 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgc 240caaatcgaag tggacgggca gctcattacc ttggagagtg gagagttcca agtatacaaa 300caaagccatt ccgccttaac cgcctttcag accgagcaaa tacaagattc ggagcattcc 360gggaagatgg ttgcgaaacg ccagttcaga atcggcgaca tagcgggcga acatacatct 420tttgacaagc ttcccgaagg cggcagggcg acatatcgcg ggacggcgtt cggttcagac 480gatgccggcg gaaaactgac ctacaccata gatttcgccg ccaagcaggg aaacggcaaa 540atcgaacatt tgaaatcgcc agaactcaat gtcgacctgg ccgccgccga tatcaagccg 600gatggaaaac gccatgccgt catcagcggt tccgtccttt acaaccaagc cgagaaaggc 660agttactccc tcggtatctt tggcggaaaa gcccaggaag ttgccggcag cgcggaagtg 720aaaaccgtaa acggcatacg ccatatcggc cttgccgcca agcaataa 768 <210> 194 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 194Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Phe Gln Thr Glu            100 105 110Gln Ile Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg Gln        115 120 125Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly Asn Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Asp            180 185 190Leu Ala Ala Ala Asp Ile Lys Pro Asp Gly Lys Arg His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Lys Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Lys Thr Val Asn Gly Ile Arg His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 195 <211> 771 <212> DNA <213> Neisseria meningitidis <400> 195tgcggatcca gcggaggggg tggtgtcgcc gccgacatcg gtgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa ggtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggtgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgttt cgactttatc 240cgccaaatcg aagtggacgg gcagctcatt accttggaga gtggagagtt ccaagtatac 300aaacaaagcc attccgcctt aaccgccttt cagaccgagc aaatacaaga ttcggagcat 360tccgggaaga tggttgcgaa acgccagttc agaatcggcg acatagcggg cgaacataca 420tcttttgaca agcttcccga aggcggcagg gcgacatatc gcgggacggc gttcggttca 480gacgatgccg gcggaaaact gacctacacc atagatttcg ccgccaagca gggaaacggc 540aaaatcgaac atttgaaatc gccagaactc aatgtcgacc tggccgccgc cgatatcaag 600ccggatggaa aacgccatgc cgtcatcagc ggttccgtcc tttacaacca agccgagaaa 660ggcagttact ccctcggtat ctttggcgga aaagcccagg aagttgccgg cagcgcggaa 720gtgaaaaccg taaacggcat acgccatatc ggccttgccg ccaagcaata a 771 <210> 196 <211> 256 <212> PRT <213> Neisseria meningitidis <400> 196Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Phe Gln Thr            100 105 110Glu Gln Ile Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg        115 120 125Gln Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys    130 135 140Leu Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser145 150 155 160Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys                165 170 175Gln Gly Asn Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val            180 185 190Asp Leu Ala Ala Ala Asp Ile Lys Pro Asp Gly Lys Arg His Ala Val        195 200 205Ile Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser    210 215 220Leu Gly Ile Phe Gly Gly Lys Ala Gln Glu Val Ala Gly Ser Ala Glu225 230 235 240Val Lys Thr Val Asn Gly Ile Arg His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 197 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 197atgagcagcg gagggggtgg tgtcgccgcc gacatcggtg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaggt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggt 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgc 240caaatcgaag tggacgggca gctcattacc ttggagagtg gagagttcca agtatacaaa 300caaagccatt ccgccttaac cgcctttcag accgagcaaa tacaagattc ggagcattcc 360gggaagatgg ttgcgaaacg ccagttcaga atcggcgaca tagcgggcga acatacatct 420tttgacaagc ttcccgaagg cggcagggcg acatatcgcg ggacggcgtt cggttcagac 480gatgccggcg gaaaactgac ctacaccata gatttcgccg ccaagcaggg aaacggcaaa 540atcgaacatt tgaaatcgcc agaactcaat gtcgacctgg ccgccgccga tatcaagccg 600gatggaaaac gccatgccgt catcagcggt tccgtccttt acaaccaagc cgagaaaggc 660agttactccc tcggtatctt tggcggaaaa gcccaggaag ttgccggcag cgcggaagtg 720aaaaccgtaa acggcatacg ccatatcggc cttgccgcca agcaataa 768 <210> 198 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 198Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Phe Gln Thr Glu            100 105 110Gln Ile Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg Gln        115 120 125Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly Asn Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Asp            180 185 190Leu Ala Ala Ala Asp Ile Lys Pro Asp Gly Lys Arg His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Lys Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Lys Thr Val Asn Gly Ile Arg His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 199 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 199tgcagcagcg gagggggtgg tgtcgccgcc gacatcggtg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaggt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggt 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgc 240caaatcgaag tggacgggca gctcattacc ttggagagtg gagagttcca agtatacaaa 300caaagccatt ccgccttaac cgcctttcag accgagcaaa tacaagattc ggagcattcc 360gggaagatgg ttgcgaaacg ccagttcaga atcggcgaca tagcgggcga acatacatct 420tttgacaagc ttcccgaagg cggcagggcg acatatcgcg ggacggcgtt cggttcagac 480gatgccggcg gaaaactgac ctacaccata gatttcgccg ccaagcaggg aaacggcaaa 540atcgaacatt tgaaatcgcc agaactcaat gtcgacctgg ccgccgccga tatcaagccg 600gatggaaaac gccatgccgt catcagcggt tccgtccttt acaaccaagc cgagaaaggc 660agttactccc tcggtatctt tggcggaaaa gcccaggaag ttgccggcag cgcggaagtg 720aaaaccgtaa acggcatacg ccatatcggc cttgccgcca agcaataa 768 <210> 200 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 200Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Phe Gln Thr Glu            100 105 110Gln Ile Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg Gln        115 120 125Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly Asn Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Asp            180 185 190Leu Ala Ala Ala Asp Ile Lys Pro Asp Gly Lys Arg His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Lys Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Lys Thr Val Asn Gly Ile Arg His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 201 <211> 771 <212> DNA <213> Neisseria meningitidis <400> 201tgcggatcca gcggaggggg tggtgtcgcc gccgacatcg gtgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa ggtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggtgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgttt cgactttatc 240cgccaaatcg aagtggacgg gcagctcatt accttggaga gtggagagtt ccaagtatac 300aaacaaagcc attccgcctt aaccgccttt cagaccgagc aaatacaaga ttcggagcat 360tccgggaaga tggttgcgaa acgccagttc agaatcggcg acatagcggg cgaacataca 420tcttttgaca agcttcccga aggcggcagg gcgacatatc gcgggacggc gttcggttca 480gacgatgccg gcggaaaact gacctacacc atagatttcg ccgccaagca gggaaacggc 540aaaatcgaac atttgaaatc gccagaactc aatgtcgacc tggccgccgc cgatatcaag 600ccggatggaa aacgccatgc cgtcatcagc ggttccgtcc tttacaacca agccgagaaa 660ggcagttact ccctcggtat ctttggcgga aaagcccagg aagttgccgg cagcgcggaa 720gtgaaaaccg taaacggcat acgccatatc ggccttgccg ccaagcaata a 771 <210> 202 <211> 256 <212> PRT <213> Neisseria meningitidis <400> 202Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Phe Gln Thr            100 105 110Glu Gln Ile Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg        115 120 125Gln Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys    130 135 140Leu Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser145 150 155 160Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys                165 170 175Gln Gly Asn Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val            180 185 190Asp Leu Ala Ala Ala Asp Ile Lys Pro Asp Gly Lys Arg His Ala Val        195 200 205Ile Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser    210 215 220Leu Gly Ile Phe Gly Gly Lys Ala Gln Glu Val Ala Gly Ser Ala Glu225 230 235 240Val Lys Thr Val Asn Gly Ile Arg His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 203 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 203atgagcagcg gagggggtgg tgtcgccgcc gacatcggtg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaggt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggt 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgc 240caaatcgaag tggacgggca gctcattacc ttggagagtg gagagttcca agtatacaaa 300caaagccatt ccgccttaac cgcctttcag accgagcaaa tacaagattc ggagcattcc 360gggaagatgg ttgcgaaacg ccagttcaga atcggcgaca tagcgggcga acatacatct 420tttgacaagc ttcccgaagg cggcagggcg acatatcgcg ggacggcgtt cggttcagac 480gatgccggcg gaaaactgac ctacaccata gatttcgccg ccaagcaggg aaacggcaaa 540atcgaacatt tgaaatcgcc agaactcaat gtcgacctgg ccgccgccga tatcaagccg 600gatggaaaac gccatgccgt catcagcggt tccgtccttt acaaccaagc cgagaaaggc 660agttactccc tcggtatctt tggcggaaaa gcccaggaag ttgccggcag cgcggaagtg 720aaaaccgtaa acggcatacg ccatatcggc cttgccgcca agcaataa 768 <210> 204 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 204Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Phe Gln Thr Glu            100 105 110Gln Ile Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg Gln        115 120 125Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly Asn Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Asp            180 185 190Leu Ala Ala Ala Asp Ile Lys Pro Asp Gly Lys Arg His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Lys Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Lys Thr Val Asn Gly Ile Arg His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 205 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 205tgcagcagcg gagggggtgg tgtcgccgcc gacatcggtg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaggt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggt 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgc 240caaatcgaag tggacgggca gctcattacc ttggagagtg gagagttcca agtatacaaa 300caaagccatt ccgccttaac cgcctttcag accgagcaaa tacaagattc ggagcattcc 360gggaagatgg ttgcgaaacg ccagttcaga atcggcgaca tagcgggcga acatacatct 420tttgacaagc ttcccgaagg cggcagggcg acatatcgcg ggacggcgtt cggttcagac 480gatgccggcg gaaaactgac ctacaccata gatttcgccg ccaagcaggg aaacggcaaa 540atcgaacatt tgaaatcgcc agaactcaat gtcgacctgg ccgccgccga tatcaagccg 600gatggaaaac gccatgccgt catcagcggt tccgtccttt acaaccaagc cgagaaaggc 660agttactccc tcggtatctt tggcggaaaa gcccaggaag ttgccggcag cgcggaagtg 720aaaaccgtaa acggcatacg ccatatcggc cttgccgcca agcaataa 768 <206> 206 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 206Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Phe Gln Thr Glu            100 105 110Gln Ile Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg Gln        115 120 125Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly Asn Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Asp            180 185 190Leu Ala Ala Ala Asp Ile Lys Pro Asp Gly Lys Arg His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Lys Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Lys Thr Val Asn Gly Ile Arg His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 207 <211> 771 <212> DNA <213> Neisseria meningitidis <400> 207tgcggatcca gcggaggggg tggtgtcgcc gccgacatcg gtgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa ggtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggtgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgttt cgactttatc 240cgccaaatcg aagtggacgg gcagctcatt accttggaga gtggagagtt ccaagtatac 300aaacaaagcc attccgcctt aaccgccttt cagaccgagc aaatacaaga ttcggagcat 360tccgggaaga tggttgcgaa acgccagttc agaatcggcg acatagcggg cgaacataca 420tcttttgaca agcttcccga aggcggcagg gcgacatatc gcgggacggc gttcggttca 480gacgatgccg gcggaaaact gacctacacc atagatttcg ccgccaagca gggaaacggc 540aaaatcgaac atttgaaatc gccagaactc aatgtcgacc tggccgccgc cgatatcaag 600ccggatggaa aacgccatgc cgtcatcagc ggttccgtcc tttacaacca agccgagaaa 660ggcagttact ccctcggtat ctttggcgga aaagcccagg aagttgccgg cagcgcggaa 720gtgaaaaccg taaacggcat acgccatatc ggccttgccg ccaagcaata a 771 <210> 208 <211> 256 <212> PRT <213> Neisseria meningitidis <400> 208Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Phe Gln Thr            100 105 110Glu Gln Ile Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg        115 120 125Gln Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys    130 135 140Leu Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser145 150 155 160Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys                165 170 175Gln Gly Asn Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val            180 185 190Asp Leu Ala Ala Ala Asp Ile Lys Pro Asp Gly Lys Arg His Ala Val        195 200 205Ile Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser    210 215 220Leu Gly Ile Phe Gly Gly Lys Ala Gln Glu Val Ala Gly Ser Ala Glu225 230 235 240Val Lys Thr Val Asn Gly Ile Arg His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 209 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 209atgagcagcg gagggggtgg tgtcgccgcc gacatcggtg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaggt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggt 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgc 240caaatcgaag tggacgggca gctcattacc ttggagagtg gagagttcca agtatacaaa 300caaagccatt ccgccttaac cgcctttcag accgagcaaa tacaagattc ggagcattcc 360gggaagatgg ttgcgaaacg ccagttcaga atcggcgaca tagcgggcga acatacatct 420tttgacaagc ttcccgaagg cggcagggcg acatatcgcg ggacggcgtt cggttcagac 480gatgccggcg gaaaactgac ctacaccata gatttcgccg ccaagcaggg aaacggcaaa 540atcgaacatt tgaaatcgcc agaactcaat gtcgacctgg ccgccgccga tatcaagccg 600gatggaaaac gccatgccgt catcagcggt tccgtccttt acaaccaagc cgagaaaggc 660agttactccc tcggtatctt tggcggaaaa gcccaggaag ttgccggcag cgcggaagtg 720aaaaccgtaa acggcatacg ccatatcggc cttgccgcca agcaataa 768 <210> 210 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 210Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Phe Gln Thr Glu            100 105 110Gln Ile Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg Gln        115 120 125Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly Asn Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Asp            180 185 190Leu Ala Ala Ala Asp Ile Lys Pro Asp Gly Lys Arg His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Lys Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Lys Thr Val Asn Gly Ile Arg His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 211 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 211tgcagcagcg gagggggtgg tgtcgccgcc gacatcggtg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaggt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggt 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgc 240caaatcgaag tggacgggca gctcattacc ttggagagtg gagagttcca agtatacaaa 300caaagccatt ccgccttaac cgcctttcag accgagcaaa tacaagattc ggagcattcc 360gggaagatgg ttgcgaaacg ccagttcaga atcggcgaca tagcgggcga acatacatct 420tttgacaagc ttcccgaagg cggcagggcg acatatcgcg ggacggcgtt cggttcagac 480gatgccggcg gaaaactgac ctacaccata gatttcgccg ccaagcaggg aaacggcaaa 540atcgaacatt tgaaatcgcc agaactcaat gtcgacctgg ccgccgccga tatcaagccg 600gatggaaaac gccatgccgt catcagcggt tccgtccttt acaaccaagc cgagaaaggc 660agttactccc tcggtatctt tggcggaaaa gcccaggaag ttgccggcag cgcggaagtg 720aaaaccgtaa acggcatacg ccatatcggt cttgccgcca agcagtaa 768 <210> 212 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 212Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Phe Gln Thr Glu            100 105 110Gln Ile Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg Gln        115 120 125Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly Asn Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Asp            180 185 190Leu Ala Ala Ala Asp Ile Lys Pro Asp Gly Lys Arg His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Lys Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Lys Thr Val Asn Gly Ile Arg His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 213 <211> 771 <212> DNA <213> Neisseria meningitidis <400> 213tgcggatcca gcggaggggg tggtgtcgcc gccgacatcg gtgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa ggtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggtgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgttt cgactttatc 240cgccaaatcg aagtggacgg gcagctcatt accttggaga gtggagagtt ccaagtatac 300aaacaaagcc attccgcctt aaccgccttt cagaccgagc aaatacaaga ttcggagcat 360tccgggaaga tggttgcgaa acgccagttc agaatcggcg acatagcggg cgaacataca 420tcttttgaca agcttcccga aggcggcagg gcgacatatc gcgggacggc gttcggttca 480gacgatgccg gcggaaaact gacctacacc atagatttcg ccgccaagca gggaaacggc 540aaaatcgaac atttgaaatc gccagaactc aatgtcgacc tggccgccgc cgatatcaag 600ccggatggaa aacgccatgc cgtcatcagc ggttccgtcc tttacaacca agccgagaaa 660ggcagttact ccctcggtat ctttggcgga aaagcccagg aagttgccgg cagcgcggaa 720gtgaaaaccg taaacggcat acgccatatc ggtcttgccg ccaagcagta a 771 <210> 214 <211> 256 <212> PRT <213> Neisseria meningitidis <400> 214Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Phe Gln Thr            100 105 110Glu Gln Ile Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg        115 120 125Gln Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys    130 135 140Leu Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser145 150 155 160Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys                165 170 175Gln Gly Asn Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val            180 185 190Asp Leu Ala Ala Ala Asp Ile Lys Pro Asp Gly Lys Arg His Ala Val        195 200 205Ile Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser    210 215 220Leu Gly Ile Phe Gly Gly Lys Ala Gln Glu Val Ala Gly Ser Ala Glu225 230 235 240Val Lys Thr Val Asn Gly Ile Arg His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 215 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 215atgagcagcg gagggggtgg tgtcgccgcc gacatcggtg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaggt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggt 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgc 240caaatcgaag tggacgggca gctcattacc ttggagagtg gagagttcca agtatacaaa 300caaagccatt ccgccttaac cgcctttcag accgagcaaa tacaagattc ggagcattcc 360gggaagatgg ttgcgaaacg ccagttcaga atcggcgaca tagcgggcga acatacatct 420tttgacaagc ttcccgaagg cggcagggcg acatatcgcg ggacggcgtt cggttcagac 480gatgccggcg gaaaactgac ctacaccata gatttcgccg ccaagcaggg aaacggcaaa 540atcgaacatt tgaaatcgcc agaactcaat gtcgacctgg ccgccgccga tatcaagccg 600gatggaaaac gccatgccgt catcagcggt tccgtccttt acaaccaagc cgagaaaggc 660agttactccc tcggtatctt tggcggaaaa gcccaggaag ttgccggcag cgcggaagtg 720aaaaccgtaa acggcatacg ccatatcggt cttgccgcca agcagtaa 768 <210> 216 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 216Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Phe Gln Thr Glu            100 105 110Gln Ile Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg Gln        115 120 125Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly Asn Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Asp            180 185 190Leu Ala Ala Ala Asp Ile Lys Pro Asp Gly Lys Arg His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Lys Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Lys Thr Val Asn Gly Ile Arg His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 217 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 217tgcagcagcg gagggggcgg tgtcgccgcc gacatcggtg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaggt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacaggca gctcattacc ttggagagcg gagagttcca agtgtacaaa 300caaagccatt ccgccttaac cgcccttcag accgagcaag tacaagactc ggagcattcc 360gggaagatgg ttgcgaaacg tcagttcaga atcggcgaca tagcgggtga acatacatct 420tttgacaagc ttcccgaagg cggcagggcg acatatcgcg ggacggcgtt cggttcagac 480gatgccggcg gaaaactgat ttacaccata gatttcgccg ctaagcaggg acacggtaaa 540atcgaacatt tgaaatcgcc agaactcaat gtcgacctgg ccgccgccga tatcaagccg 600gatgaaaaac accatgccgt catcagcggt tccgtccttt acaaccaagc cgagaaaggc 660agttactccc tcggtatctt tggcggaaaa gcccaggaag ttgccggcag cgcggaagtg 720aaaaccgtaa acggtatacg ccatatcggc cttgccgcca agcaataa 768 <210> 218 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 218Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Arg Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Leu Gln Thr Glu            100 105 110Gln Val Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg Gln        115 120 125Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Ile Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Asp            180 185 190Leu Ala Ala Ala Asp Ile Lys Pro Asp Glu Lys His His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Lys Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Lys Thr Val Asn Gly Ile Arg His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 219 <211> 771 <212> DNA <213> Neisseria meningitidis <400> 219tgcggatcca gcggaggggg cggtgtcgcc gccgacatcg gtgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa ggtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc tcaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacag gcagctcatt accttggaga gcggagagtt ccaagtgtac 300aaacaaagcc attccgcctt aaccgccctt cagaccgagc aagtacaaga ctcggagcat 360tccgggaaga tggttgcgaa acgtcagttc agaatcggcg acatagcggg tgaacataca 420tcttttgaca agcttcccga aggcggcagg gcgacatatc gcgggacggc gttcggttca 480gacgatgccg gcggaaaact gatttacacc atagatttcg ccgctaagca gggacacggt 540aaaatcgaac atttgaaatc gccagaactc aatgtcgacc tggccgccgc cgatatcaag 600ccggatgaaa aacaccatgc cgtcatcagc ggttccgtcc tttacaacca agccgagaaa 660ggcagttact ccctcggtat ctttggcgga aaagcccagg aagttgccgg cagcgcggaa 720gtgaaaaccg taaacggtat acgccatatc ggccttgccg ccaagcaata a 771 <210> 220 <211> 256 <212> PRT <213> Neisseria meningitidis <400> 220Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Arg Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Leu Gln Thr            100 105 110Glu Gln Val Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg        115 120 125Gln Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys    130 135 140Leu Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser145 150 155 160Asp Asp Ala Gly Gly Lys Leu Ile Tyr Thr Ile Asp Phe Ala Ala Lys                165 170 175Gln Gly His Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val            180 185 190Asp Leu Ala Ala Ala Asp Ile Lys Pro Asp Glu Lys His His Ala Val        195 200 205Ile Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser    210 215 220Leu Gly Ile Phe Gly Gly Lys Ala Gln Glu Val Ala Gly Ser Ala Glu225 230 235 240Val Lys Thr Val Asn Gly Ile Arg His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 221 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 221atgagcagcg gagggggcgg tgtcgccgcc gacatcggtg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaggt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctca atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacaggca gctcattacc ttggagagcg gagagttcca agtgtacaaa 300caaagccatt ccgccttaac cgcccttcag accgagcaag tacaagactc ggagcattcc 360gggaagatgg ttgcgaaacg tcagttcaga atcggcgaca tagcgggtga acatacatct 420tttgacaagc ttcccgaagg cggcagggcg acatatcgcg ggacggcgtt cggttcagac 480gatgccggcg gaaaactgat ttacaccata gatttcgccg ctaagcaggg acacggtaaa 540atcgaacatt tgaaatcgcc agaactcaat gtcgacctgg ccgccgccga tatcaagccg 600gatgaaaaac accatgccgt catcagcggt tccgtccttt acaaccaagc cgagaaaggc 660agttactccc tcggtatctt tggcggaaaa gcccaggaag ttgccggcag cgcggaagtg 720aaaaccgtaa acggtatacg ccatatcggc cttgccgcca agcaataa 768 <210> 222 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 222Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Arg Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Leu Gln Thr Glu            100 105 110Gln Val Gln Asp Ser Glu His Ser Gly Lys Met Val Ala Lys Arg Gln        115 120 125Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Glu Gly Gly Arg Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Ile Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Asp            180 185 190Leu Ala Ala Ala Asp Ile Lys Pro Asp Glu Lys His His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Ala Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Lys Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Lys Thr Val Asn Gly Ile Arg His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 223 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 223tgcagcagcg gagggggcgg tgtcgccgcc gacatcggtg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaggt ttgcagtctt taacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctta atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggaa gctcattacc ttggagagcg gagagttcca agtgtacaaa 300caaagccatt ccgccttaac cgcccttcag accgagcaag tacaagactc ggaggattcc 360gggaagatgg ttgcgaaacg ccagttcaga atcggcgaca tagcgggcga acatacatct 420tttgacaagc ttcccaaagg cggcagtgcg acatatcgcg ggacggcgtt cggttcagac 480gatgctggcg gaaaactgac ctatactata gatttcgccg ccaagcaggg acacggcaaa 540atcgaacatt tgaaatcgcc cgaactcaat gtcgagcttg ccaccgccta tatcaagccg 600gatgaaaaac gccatgccgt tatcagcggt tccgtccttt acaaccaaga cgagaaaggc 660agttactccc tcggtatctt tggcgggcaa gcccaggaag ttgccggcag cgcggaagtg 720gaaaccgcaa acggcataca ccatatcggt cttgccgcca agcagtaa 768 <210> 224 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 224Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Lys Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Leu Gln Thr Glu            100 105 110Gln Val Gln Asp Ser Glu Asp Ser Gly Lys Met Val Ala Lys Arg Gln        115 120 125Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Lys Gly Gly Ser Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Glu            180 185 190Leu Ala Thr Ala Tyr Ile Lys Pro Asp Glu Lys Arg His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Asp Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Gln Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Glu Thr Ala Asn Gly Ile His His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 225 <211> 771 <212> DNA <213> Neisseria meningitidis <400> 225tgcggatcca gcggaggggg cggtgtcgcc gccgacatcg gtgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa ggtttgcagt ctttaacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc ttaatacggg caaattgaag aacgacaagg tcagccgctt cgactttatc 240cgtcaaatcg aagtggacgg gaagctcatt accttggaga gcggagagtt ccaagtgtac 300aaacaaagcc attccgcctt aaccgccctt cagaccgagc aagtacaaga ctcggaggat 360tccgggaaga tggttgcgaa acgccagttc agaatcggcg acatagcggg cgaacataca 420tcttttgaca agcttcccaa aggcggcagt gcgacatatc gcgggacggc gttcggttca 480gacgatgctg gcggaaaact gacctatact atagatttcg ccgccaagca gggacacggc 540aaaatcgaac atttgaaatc gcccgaactc aatgtcgagc ttgccaccgc ctatatcaag 600ccggatgaaa aacgccatgc cgttatcagc ggttccgtcc tttacaacca agacgagaaa 660ggcagttact ccctcggtat ctttggcggg caagcccagg aagttgccgg cagcgcggaa 720gtggaaaccg caaacggcat acaccatatc ggtcttgccg ccaagcagta a 771 <210> 226 <211> 256 <212> PRT <213> Neisseria meningitidis <400> 226Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Lys Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Leu Gln Thr            100 105 110Glu Gln Val Gln Asp Ser Glu Asp Ser Gly Lys Met Val Ala Lys Arg        115 120 125Gln Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys    130 135 140Leu Pro Lys Gly Gly Ser Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser145 150 155 160Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys                165 170 175Gln Gly His Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val            180 185 190Glu Leu Ala Thr Ala Tyr Ile Lys Pro Asp Glu Lys Arg His Ala Val        195 200 205Ile Ser Gly Ser Val Leu Tyr Asn Gln Asp Glu Lys Gly Ser Tyr Ser    210 215 220Leu Gly Ile Phe Gly Gly Gln Ala Gln Glu Val Ala Gly Ser Ala Glu225 230 235 240Val Glu Thr Ala Asn Gly Ile His His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 227 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 227atgagcagcg gagggggcgg tgtcgccgcc gacatcggtg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaggt ttgcagtctt taacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctta atacgggcaa attgaagaac gacaaggtca gccgcttcga ctttatccgt 240caaatcgaag tggacgggaa gctcattacc ttggagagcg gagagttcca agtgtacaaa 300caaagccatt ccgccttaac cgcccttcag accgagcaag tacaagactc ggaggattcc 360gggaagatgg ttgcgaaacg ccagttcaga atcggcgaca tagcgggcga acatacatct 420tttgacaagc ttcccaaagg cggcagtgcg acatatcgcg ggacggcgtt cggttcagac 480gatgctggcg gaaaactgac ctatactata gatttcgccg ccaagcaggg acacggcaaa 540atcgaacatt tgaaatcgcc cgaactcaat gtcgagcttg ccaccgccta tatcaagccg 600gatgaaaaac gccatgccgt tatcagcggt tccgtccttt acaaccaaga cgagaaaggc 660agttactccc tcggtatctt tggcgggcaa gcccaggaag ttgccggcag cgcggaagtg 720gaaaccgcaa acggcataca ccatatcggt cttgccgcca agcagtaa 768 <210> 228 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 228Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Gly Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Lys Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Leu Gln Thr Glu            100 105 110Gln Val Gln Asp Ser Glu Asp Ser Gly Lys Met Val Ala Lys Arg Gln        115 120 125Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Lys Gly Gly Ser Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Glu            180 185 190Leu Ala Thr Ala Tyr Ile Lys Pro Asp Glu Lys Arg His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Asp Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Gln Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Glu Thr Ala Asn Gly Ile His His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 229 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 229tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctta atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca agtgtacaaa 300caaagccatt ccgccttaac cgcccttcag accgagcaag aacaagatcc agagcattcc 360gggaagatgg ttgcgaaacg ccggttcaaa atcggcgaca tagcgggcga acatacatct 420tttgacaagc ttcccaaaga cgtcatggcg acatatcgcg ggacggcgtt cggttcagac 480gatgccggcg gaaaactgac ctatactata gattttgctg ccaaacaggg acacggcaaa 540atcgaacatt tgaaatcgcc cgaactcaat gtcgagcttg ccaccgccta tatcaagccg 600gatgaaaaac accatgccgt catcagcggt tccgtccttt acaatcaaga cgagaaaggc 660agttactccc tcggtatctt tggcgggcaa gcccaggaag ttgccggcag cgcggaagtg 720gaaaccgcaa acggcataca ccatatcggt cttgccgcca agcaataa 768 <210> 230 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 230Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Leu Gln Thr Glu            100 105 110Gln Glu Gln Asp Pro Glu His Ser Gly Lys Met Val Ala Lys Arg Arg        115 120 125Phe Lys Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Lys Asp Val Met Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Glu            180 185 190Leu Ala Thr Ala Tyr Ile Lys Pro Asp Glu Lys His His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Asp Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Gln Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Glu Thr Ala Asn Gly Ile His His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 231 <211> 771 <212> DNA <213> Neisseria meningitidis <400> 231tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc ttaatacggg caaattgaag aacgacaagg tcagccgttt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaagtgtac 300aaacaaagcc attccgcctt aaccgccctt cagaccgagc aagaacaaga tccagagcat 360tccgggaaga tggttgcgaa acgccggttc aaaatcggcg acatagcggg cgaacataca 420tcttttgaca agcttcccaa agacgtcatg gcgacatatc gcgggacggc gttcggttca 480gacgatgccg gcggaaaact gacctatact atagattttg ctgccaaaca gggacacggc 540aaaatcgaac atttgaaatc gcccgaactc aatgtcgagc ttgccaccgc ctatatcaag 600ccggatgaaa aacaccatgc cgtcatcagc ggttccgtcc tttacaatca agacgagaaa 660ggcagttact ccctcggtat ctttggcggg caagcccagg aagttgccgg cagcgcggaa 720gtggaaaccg caaacggcat acaccatatc ggtcttgccg ccaagcaata a 771 <210> 232 <211> 256 <212> PRT <213> Neisseria meningitidis <400> 232Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Leu Gln Thr            100 105 110Glu Gln Glu Gln Asp Pro Glu His Ser Gly Lys Met Val Ala Lys Arg        115 120 125Arg Phe Lys Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys    130 135 140Leu Pro Lys Asp Val Met Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser145 150 155 160Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys                165 170 175Gln Gly His Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val            180 185 190Glu Leu Ala Thr Ala Tyr Ile Lys Pro Asp Glu Lys His His Ala Val        195 200 205Ile Ser Gly Ser Val Leu Tyr Asn Gln Asp Glu Lys Gly Ser Tyr Ser    210 215 220Leu Gly Ile Phe Gly Gly Gln Ala Gln Glu Val Ala Gly Ser Ala Glu225 230 235 240Val Glu Thr Ala Asn Gly Ile His His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 233 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 233atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctta atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca agtgtacaaa 300caaagccatt ccgccttaac cgcccttcag accgagcaag aacaagatcc agagcattcc 360gggaagatgg ttgcgaaacg ccggttcaaa atcggcgaca tagcgggcga acatacatct 420tttgacaagc ttcccaaaga cgtcatggcg acatatcgcg ggacggcgtt cggttcagac 480gatgccggcg gaaaactgac ctatactata gattttgctg ccaaacaggg acacggcaaa 540atcgaacatt tgaaatcgcc cgaactcaat gtcgagcttg ccaccgccta tatcaagccg 600gatgaaaaac accatgccgt catcagcggt tccgtccttt acaatcaaga cgagaaaggc 660agttactccc tcggtatctt tggcgggcaa gcccaggaag ttgccggcag cgcggaagtg 720gaaaccgcaa acggcataca ccatatcggt cttgccgcca agcaataa 768 <210> 234 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 234Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Leu Gln Thr Glu            100 105 110Gln Glu Gln Asp Pro Glu His Ser Gly Lys Met Val Ala Lys Arg Arg        115 120 125Phe Lys Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Lys Asp Val Met Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Glu            180 185 190Leu Ala Thr Ala Tyr Ile Lys Pro Asp Glu Lys His His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Asp Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Gln Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Glu Thr Ala Asn Gly Ile His His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 235 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 235tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctta atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca agtgtacaaa 300caaagccatt ccgccttaac cgcccttcag accgagcaag aacaagatcc agagcattcc 360gggaagatgg ttgcgaaacg ccggttcaaa atcggcgaca tagcgggcga acatacatct 420tttgacaagc ttcccaaaga cgtcatggcg acatatcgcg ggacggcgtt cggttcagac 480gatgccggcg gaaaactgac ctatactata gattttgctg ccaaacaggg acacggcaaa 540atcgaacatt tgaaatcgcc cgaactcaat gtcgagcttg ccaccgccta tatcaagccg 600gatgaaaaac accatgccgt catcagcggt tccgtccttt acaatcaaga cgagaaaggc 660agttactccc tcggtatctt tggcgggcaa gcccaggaag ttgccggcag cgcggaagtg 720gaaaccgcaa acggcataca ccatatcggt cttgccgcca agcaataa 768 <210> 236 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 236Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Leu Gln Thr Glu            100 105 110Gln Glu Gln Asp Pro Glu His Ser Gly Lys Met Val Ala Lys Arg Arg        115 120 125Phe Lys Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Lys Asp Val Met Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Glu            180 185 190Leu Ala Thr Ala Tyr Ile Lys Pro Asp Glu Lys His His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Asp Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Gln Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Glu Thr Ala Asn Gly Ile His His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 237 <211> 771 <212> DNA <213> Neisseria meningitidis <400> 237tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc ttaatacggg caaattgaag aacgacaagg tcagccgttt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaagtgtac 300aaacaaagcc attccgcctt aaccgccctt cagaccgagc aagaacaaga tccagagcat 360tccgggaaga tggttgcgaa acgccggttc aaaatcggcg acatagcggg cgaacataca 420tcttttgaca agcttcccaa agacgtcatg gcgacatatc gcgggacggc gttcggttca 480gacgatgccg gcggaaaact gacctatact atagattttg ctgccaaaca gggacacggc 540aaaatcgaac atttgaaatc gcccgaactc aatgtcgagc ttgccaccgc ctatatcaag 600ccggatgaaa aacaccatgc cgtcatcagc ggttccgtcc tttacaatca agacgagaaa 660ggcagttact ccctcggtat ctttggcggg caagcccagg aagttgccgg cagcgcggaa 720gtggaaaccg caaacggcat acaccatatc ggtcttgccg ccaagcaata a 771 <210> 238 <211> 256 <212> PRT <213> Neisseria meningitidis <400> 238Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Leu Gln Thr            100 105 110Glu Gln Glu Gln Asp Pro Glu His Ser Gly Lys Met Val Ala Lys Arg        115 120 125Arg Phe Lys Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys    130 135 140Leu Pro Lys Asp Val Met Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser145 150 155 160Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys                165 170 175Gln Gly His Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val            180 185 190Glu Leu Ala Thr Ala Tyr Ile Lys Pro Asp Glu Lys His His Ala Val        195 200 205Ile Ser Gly Ser Val Leu Tyr Asn Gln Asp Glu Lys Gly Ser Tyr Ser    210 215 220Leu Gly Ile Phe Gly Gly Gln Ala Gln Glu Val Ala Gly Ser Ala Glu225 230 235 240Val Glu Thr Ala Asn Gly Ile His His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 239 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 239atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctta atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca agtgtacaaa 300caaagccatt ccgccttaac cgcccttcag accgagcaag aacaagatcc agagcattcc 360gggaagatgg ttgcgaaacg ccggttcaaa atcggcgaca tagcgggcga acatacatct 420tttgacaagc ttcccaaaga cgtcatggcg acatatcgcg ggacggcgtt cggttcagac 480gatgccggcg gaaaactgac ctatactata gattttgctg ccaaacaggg acacggcaaa 540atcgaacatt tgaaatcgcc cgaactcaat gtcgagcttg ccaccgccta tatcaagccg 600gatgaaaaac accatgccgt catcagcggt tccgtccttt acaatcaaga cgagaaaggc 660agttactccc tcggtatctt tggcgggcaa gcccaggaag ttgccggcag cgcggaagtg 720gaaaccgcaa acggcataca ccatatcggt cttgccgcca agcaataa 768 <210> 240 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 240Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Leu Gln Thr Glu            100 105 110Gln Glu Gln Asp Pro Glu His Ser Gly Lys Met Val Ala Lys Arg Arg        115 120 125Phe Lys Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Lys Asp Val Met Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Glu            180 185 190Leu Ala Thr Ala Tyr Ile Lys Pro Asp Glu Lys His His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Asp Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Gln Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Glu Thr Ala Asn Gly Ile His His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 241 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 241tgcagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctta atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca agtgtacaaa 300caaagccatt ccgccttaac cgcccttcag accgagcaag aacaagatcc agagcattcc 360gggaagatgg ttgcgaaacg ccggttcaaa atcggcgaca tagcgggcga acatacatct 420tttgacaagc ttcccaaaga cgtcatggcg acatatcgcg ggacggcgtt cggttcagac 480gatgccggcg gaaaactgac ctatactata gattttgctg ccaaacaggg acacggcaaa 540atcgaacatt tgaaatcgcc cgaactcaat gtcgagcttg ccaccgccta tatcaagccg 600gatgaaaaac accatgccgt catcagcggt tccgtccttt acaatcaaga cgagaaaggc 660agttactccc tcggtatctt tggcgggcaa gcccaggaag ttgccggcag cgcggaagtg 720gaaaccgcaa acggcataca ccatatcggt cttgccgcca agcaa 765 <210> 242 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 242Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Leu Gln Thr Glu            100 105 110Gln Glu Gln Asp Pro Glu His Ser Gly Lys Met Val Ala Lys Arg Arg        115 120 125Phe Lys Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Lys Asp Val Met Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Glu            180 185 190Leu Ala Thr Ala Tyr Ile Lys Pro Asp Glu Lys His His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Asp Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Gln Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Glu Thr Ala Asn Gly Ile His His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 243 <211> 768 <212> DNA <213> Neisseria meningitidis <400> 243tgcggatcca gcggaggcgg cggtgtcgcc gccgacatcg gcgcggggct tgccgatgca 60ctaaccgcac cgctcgacca taaagacaaa agtttgcagt ctttgacgct ggatcagtcc 120gtcaggaaaa acgagaaact gaagctggcg gcacaaggtg cggaaaaaac ttatggaaac 180ggcgacagcc ttaatacggg caaattgaag aacgacaagg tcagccgttt cgactttatc 240cgtcaaatcg aagtggacgg gcagctcatt accttggaga gcggagagtt ccaagtgtac 300aaacaaagcc attccgcctt aaccgccctt cagaccgagc aagaacaaga tccagagcat 360tccgggaaga tggttgcgaa acgccggttc aaaatcggcg acatagcggg cgaacataca 420tcttttgaca agcttcccaa agacgtcatg gcgacatatc gcgggacggc gttcggttca 480gacgatgccg gcggaaaact gacctatact atagattttg ctgccaaaca gggacacggc 540aaaatcgaac atttgaaatc gcccgaactc aatgtcgagc ttgccaccgc ctatatcaag 600ccggatgaaa aacaccatgc cgtcatcagc ggttccgtcc tttacaatca agacgagaaa 660ggcagttact ccctcggtat ctttggcggg caagcccagg aagttgccgg cagcgcggaa 720gtggaaaccg caaacggcat acaccatatc ggtcttgccg ccaagcaa 768 <210> 244 <211> 256 <212> PRT <213> Neisseria meningitidis <400> 244Cys Gly Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly1 5 10 15Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu            20 25 30Gln Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys        35 40 45Leu Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu    50 55 60Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile65 70 75 80Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu                85 90 95Phe Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Leu Gln Thr            100 105 110Glu Gln Glu Gln Asp Pro Glu His Ser Gly Lys Met Val Ala Lys Arg        115 120 125Arg Phe Lys Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys    130 135 140Leu Pro Lys Asp Val Met Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser145 150 155 160Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys                165 170 175Gln Gly His Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val            180 185 190Glu Leu Ala Thr Ala Tyr Ile Lys Pro Asp Glu Lys His His Ala Val        195 200 205Ile Ser Gly Ser Val Leu Tyr Asn Gln Asp Glu Lys Gly Ser Tyr Ser    210 215 220Leu Gly Ile Phe Gly Gly Gln Ala Gln Glu Val Ala Gly Ser Ala Glu225 230 235 240Val Glu Thr Ala Asn Gly Ile His His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 245 <211> 765 <212> DNA <213> Neisseria meningitidis <400> 245atgagcagcg gaggcggcgg tgtcgccgcc gacatcggcg cggggcttgc cgatgcacta 60accgcaccgc tcgaccataa agacaaaagt ttgcagtctt tgacgctgga tcagtccgtc 120aggaaaaacg agaaactgaa gctggcggca caaggtgcgg aaaaaactta tggaaacggc 180gacagcctta atacgggcaa attgaagaac gacaaggtca gccgtttcga ctttatccgt 240caaatcgaag tggacgggca gctcattacc ttggagagcg gagagttcca agtgtacaaa 300caaagccatt ccgccttaac cgcccttcag accgagcaag aacaagatcc agagcattcc 360gggaagatgg ttgcgaaacg ccggttcaaa atcggcgaca tagcgggcga acatacatct 420tttgacaagc ttcccaaaga cgtcatggcg acatatcgcg ggacggcgtt cggttcagac 480gatgccggcg gaaaactgac ctatactata gattttgctg ccaaacaggg acacggcaaa 540atcgaacatt tgaaatcgcc cgaactcaat gtcgagcttg ccaccgccta tatcaagccg 600gatgaaaaac accatgccgt catcagcggt tccgtccttt acaatcaaga cgagaaaggc 660agttactccc tcggtatctt tggcgggcaa gcccaggaag ttgccggcag cgcggaagtg 720gaaaccgcaa acggcataca ccatatcggt cttgccgcca agcaa 765 <210> 246 <211> 255 <212> PRT <213> Neisseria meningitidis <400> 246Met Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Ala Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Ser Leu Gln            20 25 30Ser Leu Thr Leu Asp Gln Ser Val Arg Lys Asn Glu Lys Leu Lys Leu        35 40 45Ala Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Leu Gln Thr Glu            100 105 110Gln Glu Gln Asp Pro Glu His Ser Gly Lys Met Val Ala Lys Arg Arg        115 120 125Phe Lys Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Lys Asp Val Met Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Glu            180 185 190Leu Ala Thr Ala Tyr Ile Lys Pro Asp Glu Lys His His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Asp Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Gly Gln Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Glu Thr Ala Asn Gly Ile His His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 247 <211> 783 <212> DNA <213> Neisseria meningitidis <400> 247tgcagcagcg gaggcggcgg aagcggaggc ggcggtgtca ccgccgacat cggcacgggg 60cttgccgatg cactaactgc gccgctcgac cataaagaca aaggcttgaa atccctgaca 120ttggaagact ccatttccca aaacggaaca ctgaccctgt cggcacaagg tgcggaaaaa 180acttatggaa acggcgacag ccttaatacg ggcaaattga agaacgacaa ggtcagccgt 240ttcgacttta tccgtcaaat cgaagtggac gggcagctca ttaccttgga gagcggagag 300ttccaagtgt acaaacaaag ccattccgcc ttaaccgccc ttcagaccga gcaagaacaa 360gatccagagc attccgagaa gatggttgcg aaacgccggt tcagaatcgg cgacatagcg 420ggcgaacata catcttttga caagcttccc aaagacgtca tggcgacata tcgcgggacg 480gcgttcggtt cagacgatgc cggcggaaaa ctgacctata ctatagattt tgctgccaaa 540cagggacacg gcaaaatcga acatttgaaa tcgccggaac tcaatgtcga tctggccgtc 600gcctatatca agccggatga aaaacaccat gccgtcatca gcggttccgt tctttacaac 660caagacgaga aaggcagtta ctccctcggt atctttggcg aaaaagccca ggaagttgcc 720ggcagcgcgg aagtggaaac cgcaaacggc atacaccata tcggtcttgc cgccaagcag 780taa 783 <210> 248 <211> 260 <212> PRT <213> Neisseria meningitidis <400> 248Cys Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Val Thr Ala Asp1 5 10 15Ile Gly Thr Gly Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys            20 25 30Asp Lys Gly Leu Lys Ser Leu Thr Leu Glu Asp Ser Ile Ser Gln Asn        35 40 45Gly Thr Leu Thr Leu Ser Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn    50 55 60Gly Asp Ser Leu Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg65 70 75 80Phe Asp Phe Ile Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu                85 90 95Glu Ser Gly Glu Phe Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr            100 105 110Ala Leu Gln Thr Glu Gln Glu Gln Asp Pro Glu His Ser Glu Lys Met        115 120 125Val Ala Lys Arg Arg Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr    130 135 140Ser Phe Asp Lys Leu Pro Lys Asp Val Met Ala Thr Tyr Arg Gly Thr145 150 155 160Ala Phe Gly Ser Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp                165 170 175Phe Ala Ala Lys Gln Gly His Gly Lys Ile Glu His Leu Lys Ser Pro            180 185 190Glu Leu Asn Val Asp Leu Ala Val Ala Tyr Ile Lys Pro Asp Glu Lys        195 200 205His His Ala Val Ile Ser Gly Ser Val Leu Tyr Asn Gln Asp Glu Lys    210 215 220Gly Ser Tyr Ser Leu Gly Ile Phe Gly Glu Lys Ala Gln Glu Val Ala225 230 235 240Gly Ser Ala Glu Val Glu Thr Ala Asn Gly Ile His His Ile Gly Leu                245 250 255Ala Ala Lys Gln            260 <210> 249 <211> 786 <212> DNA <213> Neisseria meningitidis <400> 249tgcggatcca gcggaggcgg cggaagcgga ggcggcggtg tcaccgccga catcggcacg 60gggcttgccg atgcactaac tgcgccgctc gaccataaag acaaaggctt gaaatccctg 120acattggaag actccatttc ccaaaacgga acactgaccc tgtcggcaca aggtgcggaa 180aaaacttatg gaaacggcga cagccttaat acgggcaaat tgaagaacga caaggtcagc 240cgtttcgact ttatccgtca aatcgaagtg gacgggcagc tcattacctt ggagagcgga 300gagttccaag tgtacaaaca aagccattcc gccttaaccg cccttcagac cgagcaagaa 360caagatccag agcattccga gaagatggtt gcgaaacgcc ggttcagaat cggcgacata 420gcgggcgaac atacatcttt tgacaagctt cccaaagacg tcatggcgac atatcgcggg 480acggcgttcg gttcagacga tgccggcgga aaactgacct atactataga ttttgctgcc 540aaacagggac acggcaaaat cgaacatttg aaatcgccgg aactcaatgt cgatctggcc 600gtcgcctata tcaagccgga tgaaaaacac catgccgtca tcagcggttc cgttctttac 660aaccaagacg agaaaggcag ttactccctc ggtatctttg gcgaaaaagc ccaggaagtt 720gccggcagcg cggaagtgga aaccgcaaac ggcatacacc atatcggtct tgccgccaag 780cagtaa 786 <210> 250 <211> 261 <212> PRT <213> Neisseria meningitidis <400> 250Cys Gly Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Val Thr Ala1 5 10 15Asp Ile Gly Thr Gly Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His            20 25 30Lys Asp Lys Gly Leu Lys Ser Leu Thr Leu Glu Asp Ser Ile Ser Gln        35 40 45Asn Gly Thr Leu Thr Leu Ser Ala Gln Gly Ala Glu Lys Thr Tyr Gly    50 55 60Asn Gly Asp Ser Leu Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser65 70 75 80Arg Phe Asp Phe Ile Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr                85 90 95Leu Glu Ser Gly Glu Phe Gln Val Tyr Lys Gln Ser His Ser Ala Leu            100 105 110Thr Ala Leu Gln Thr Glu Gln Glu Gln Asp Pro Glu His Ser Glu Lys        115 120 125Met Val Ala Lys Arg Arg Phe Arg Ile Gly Asp Ile Ala Gly Glu His    130 135 140Thr Ser Phe Asp Lys Leu Pro Lys Asp Val Met Ala Thr Tyr Arg Gly145 150 155 160Thr Ala Phe Gly Ser Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile                165 170 175Asp Phe Ala Ala Lys Gln Gly His Gly Lys Ile Glu His Leu Lys Ser            180 185 190Pro Glu Leu Asn Val Asp Leu Ala Val Ala Tyr Ile Lys Pro Asp Glu        195 200 205Lys His His Ala Val Ile Ser Gly Ser Val Leu Tyr Asn Gln Asp Glu    210 215 220Lys Gly Ser Tyr Ser Leu Gly Ile Phe Gly Glu Lys Ala Gln Glu Val225 230 235 240Ala Gly Ser Ala Glu Val Glu Thr Ala Asn Gly Ile His His Ile Gly                245 250 255Leu Ala Ala Lys Gln            260 <210> 251 <211> 783 <212> DNA <213> Neisseria meningitidis <400> 251atgagcagcg gaggcggcgg aagcggaggc ggcggtgtca ccgccgacat cggcacgggg 60cttgccgatg cactaactgc gccgctcgac cataaagaca aaggcttgaa atccctgaca 120ttggaagact ccatttccca aaacggaaca ctgaccctgt cggcacaagg tgcggaaaaa 180acttatggaa acggcgacag ccttaatacg ggcaaattga agaacgacaa ggtcagccgt 240ttcgacttta tccgtcaaat cgaagtggac gggcagctca ttaccttgga gagcggagag 300ttccaagtgt acaaacaaag ccattccgcc ttaaccgccc ttcagaccga gcaagaacaa 360gatccagagc attccgagaa gatggttgcg aaacgccggt tcagaatcgg cgacatagcg 420ggcgaacata catcttttga caagcttccc aaagacgtca tggcgacata tcgcgggacg 480gcgttcggtt cagacgatgc cggcggaaaa ctgacctata ctatagattt tgctgccaaa 540cagggacacg gcaaaatcga acatttgaaa tcgccggaac tcaatgtcga tctggccgtc 600gcctatatca agccggatga aaaacaccat gccgtcatca gcggttccgt tctttacaac 660caagacgaga aaggcagtta ctccctcggt atctttggcg aaaaagccca ggaagttgcc 720ggcagcgcgg aagtggaaac cgcaaacggc atacaccata tcggtcttgc cgccaagcag 780taa 783 <210> 252 <211> 260 <212> PRT <213> Neisseria meningitidis <400> 252Met Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Val Thr Ala Asp1 5 10 15Ile Gly Thr Gly Leu Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys            20 25 30Asp Lys Gly Leu Lys Ser Leu Thr Leu Glu Asp Ser Ile Ser Gln Asn        35 40 45Gly Thr Leu Thr Leu Ser Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn    50 55 60Gly Asp Ser Leu Asn Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg65 70 75 80Phe Asp Phe Ile Arg Gln Ile Glu Val Asp Gly Gln Leu Ile Thr Leu                85 90 95Glu Ser Gly Glu Phe Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr            100 105 110Ala Leu Gln Thr Glu Gln Glu Gln Asp Pro Glu His Ser Glu Lys Met        115 120 125Val Ala Lys Arg Arg Phe Arg Ile Gly Asp Ile Ala Gly Glu His Thr    130 135 140Ser Phe Asp Lys Leu Pro Lys Asp Val Met Ala Thr Tyr Arg Gly Thr145 150 155 160Ala Phe Gly Ser Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp                165 170 175Phe Ala Ala Lys Gln Gly His Gly Lys Ile Glu His Leu Lys Ser Pro            180 185 190Glu Leu Asn Val Asp Leu Ala Val Ala Tyr Ile Lys Pro Asp Glu Lys        195 200 205His His Ala Val Ile Ser Gly Ser Val Leu Tyr Asn Gln Asp Glu Lys    210 215 220Gly Ser Tyr Ser Leu Gly Ile Phe Gly Glu Lys Ala Gln Glu Val Ala225 230 235 240Gly Ser Ala Glu Val Glu Thr Ala Asn Gly Ile His His Ile Gly Leu                245 250 255Ala Ala Lys Gln            260 <210> 253 <211> 390 <212> DNA <213> Neisseria meningitidis <400> 253gacagcctga taaaccaacg ctccttcctt gtcagcggtt tgggcggaga acataccgcc 60ttcaaccaac tgcctgacgg caaagccgag tatcacggca aagcattcag ctccgacgat 120gctggcggaa aactgaccta taccatagat ttcgccgcca aacagggaca cggcaaaatc 180gaacacctga aaacacccga gcaaaatgtc gagcttgccg ccgccgaact caaagcagat 240gaaaaatcac acgccgtcat tttgggcgac acgcgctacg gcagcgaaga aaaaggcact 300taccacctcg cccttttcgg cgaccgcgcc caagaaatcg ccggctcggc aaccgtgaag 360ataggggaaa aggttcacga aatcggcatc 390 <210> 254 <211> 10 <212> PRT <213> Neisseria meningitidis <220> <221> MISC_FEATURE (222) (5) .. (5) <223> Xaa equals any of the naturally occurring L-amino acids <400> 254Ala Asp Ile Gly Xaa Gly Leu Ala Asp Ala1 5 10 <210> 255 <211> 10 <212> PRT <213> Neisseria meningitidis <220> <221> MISC_FEATURE (222) (3) .. (3) <223> Xaa equals any of the naturally occurring L-amino acids <400> 255Ile Gly Xaa Gly Leu Ala Asp Ala Leu Thr1 5 10 <210> 256 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 256Ser Leu Asn Thr Gly Lys Leu Lys Asn Asp1 5 10 <210> 257 <211> 17 <212> PRT <213> Neisseria meningitidis <220> <221> MISC_FEATURE (222) (12) .. (12) <223> Xaa equals any of the naturally occurring L-amino acids <400> 257Ser Leu Asn Thr Gly Lys Leu Lys Asn Asp Lys Xaa Ser Arg Phe Asp1 5 10 15Phe     <210> 258 <211> 9 <212> PRT <213> Neisseria meningitidis <220> <221> MISC_FEATURE (222) (6) .. (6) <223> Xaa equals any of the naturally occurring L-amino acids <400> 258Ser Gly Glu Phe Gln Xaa Tyr Lys Gln1 5 <210> 259 <211> 8 <212> PRT <213> Neisseria meningitidis <220> <221> MISC_FEATURE (222) (6) .. (6) <223> Xaa equals any of the naturally occurring L-amino acids <400> 259Ile Glu His Leu Lys Xaa Pro Glu1 5 <210> 260 <211> 10 <212> PRT <213> Neisseria meningitidis <220> <221> MISC_FEATURE (222) (10) .. (10) <223> Xaa equals any of the naturally occurring L-amino acids <400> 260Gly Gly Gly Val Ala Ala Asp Ile Gly Xaa1 5 10 <210> 261 <211> 9 <212> PRT <213> Neisseria meningitidis <400> 261Ser Gly Glu Phe Gln Ile Tyr Lys Gln1 5 <210> 262 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 262His Ser Ala Val Val Ala Leu Gln Ile Glu1 5 10 <210> 263 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 263Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp1 5 10 <210> 264 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 264Ser Leu Ile Asn Gln Arg Ser Phe Leu Val1 5 10 <210> 265 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 265Ser Gly Leu Gly Gly Glu His Thr Ala Phe1 5 10 <210> 266 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 266Gly Glu His Thr Ala Phe Asn Gln Leu Pro1 5 10 <210> 267 <211> 11 <212> PRT <213> Neisseria meningitidis <400> 267Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His1 5 10 <210> 268 <211> 34 <212> PRT <213> Neisseria meningitidis <400> 268Glu Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg1 5 10 15Ser Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln            20 25 30Leu pro         <210> 269 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 269Gly Lys Ala Glu Tyr His Gly Lys Ala Phe1 5 10 <210> 270 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 270Tyr His Gly Lys Ala Phe Ser Ser Asp Asp1 5 10 <210> 271 <211> 14 <212> PRT <213> Neisseria meningitidis <400> 271Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp1 5 10 <210> 272 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 272Ile Glu His Leu Lys Thr Pro Glu Gln Asn1 5 10 <210> 273 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 273Lys Thr Pro Glu Gln Asn Val Glu Leu Ala1 5 10 <210> 274 <211> 14 <212> PRT <213> Neisseria meningitidis <400> 274Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu Ala1 5 10 <210> 275 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 275Ala Glu Leu Lys Ala Asp Glu Lys Ser His1 5 10 <210> 276 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 276Ala Val Ile Leu Gly Asp Thr Arg Tyr Gly1 5 10 <210> 277 <211> 20 <212> PRT <213> Neisseria meningitidis <400> 277Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu Gly Asp1 5 10 15Thr Arg Tyr Gly            20 <210> 278 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 278Glu Glu Lys Gly Thr Tyr His Leu Ala Leu1 5 10 <210> 279 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 279Leu Ile Thr Leu Glu Ser Gly Glu Phe Gln1 5 10 <210> 280 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 280Ser Ala Leu Thr Ala Leu Gln Thr Glu Gln1 5 10 <210> 281 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 281Phe Gln Val Tyr Lys Gln Ser His Ser Ala1 5 10 <210> 282 <211> 26 <212> PRT <213> Neisseria meningitidis <400> 282Leu Ile Thr Leu Glu Ser Gly Glu Phe Gln Val Tyr Lys Gln Ser His1 5 10 15Ser Ala Leu Thr Ala Leu Gln Thr Glu Gln            20 25 <210> 283 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 283Ile Gly Asp Ile Ala Gly Glu His Thr Ser1 5 10 <210> 284 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 284Glu His Thr Ser Phe Asp Lys Leu Pro Lys1 5 10 <210> 285 <211> 16 <212> PRT <213> Neisseria meningitidis <400> 285Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu Pro Lys1 5 10 15 <210> 286 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 286Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser1 5 10 <210> 287 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 287Asp Asp Ala Gly Gly Lys Leu Thr Tyr Thr1 5 10 <210> 288 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 288Ile Asp Phe Ala Ala Lys Gln Gly His Gly1 5 10 <210> 289 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 289Lys Ile Glu His Leu Lys Ser Pro Glu Leu1 5 10 <210> 290 <211> 42 <212> PRT <213> Neisseria meningitidis <400> 290Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp Asp Ala Gly Gly Lys1 5 10 15Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln Gly His Gly Lys Ile            20 25 30Glu His Leu Lys Ser Pro Glu Leu Asn Val        35 40 <210> 291 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 291His Ala Val Ile Ser Gly Ser Val Leu Tyr1 5 10 <210> 292 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 292Lys Gly Ser Tyr Ser Leu Gly Ile Phe Gly1 5 10 <210> 293 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 293Val Leu Tyr Asn Gln Asp Glu Lys Gly Ser1 5 10 <210> 294 <211> 24 <212> PRT <213> Neisseria meningitidis <400> 294His Ala Val Ile Ser Gly Ser Val Leu Tyr Asn Gln Asp Glu Lys Gly1 5 10 15Ser Tyr Ser Leu Gly Ile Phe Gly            20 <210> 295 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 295Ala Gln Glu Val Ala Gly Ser Ala Glu Val1 5 10 <210> 296 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 296Ile His His Ile Gly Leu Ala Ala Lys Gln1 5 10 <210> 297 <211> 10 <212> PRT <213> Neisseria meningitidis <400> 297Val Glu Thr Ala Asn Gly Ile His His Ile1 5 10 <210> 298 <211> 25 <212> PRT <213> Neisseria meningitidis <400> 298Ala Gln Glu Val Ala Gly Ser Ala Glu Val Glu Thr Ala Asn Gly Ile1 5 10 15His His Ile Gly Leu Ala Ala Lys Gln            20 25 <210> 299 <211> 22 <212> PRT <213> Neisseria meningitidis <400> 299Val Ala Gly Ser Ala Glu Val Glu Thr Ala Asn Gly Ile His His Ile1 5 10 15Gly Leu Ala Ala Lys Gln            20 <210> 300 <211> 254 <212> PRT <213> Neisseria meningitidis <220> <221> MISC_FEATURE (222) (9) .. (9) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (14) .. (14) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (22) .. (22) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (24) .. (24) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (26) .. (26) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (30) .. (30) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (32) .. (32) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (37) .. (37) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (38) .. (38) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (40) .. (40) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (41) .. (41) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (42) .. (42) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (44) .. (44) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (45) .. (45) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (47) .. (47) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (49) .. (49) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (57) .. (57) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (58) .. (58) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (59) .. (59) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (73) .. (73) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (79) .. (79) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (80) .. (80) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (81) .. (81) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (83) .. (83) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (87) .. (87) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (88) .. (88) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (92) .. (92) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (98) .. (98) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (102) .. (102) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (106) .. (106) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (107) .. (107) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (111) .. (111) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (113) .. (113) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (114) .. (114) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (115) .. (115) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE 116 (116) .. (116) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <117> (117) .. (117) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <118> (118) .. (118) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (119) .. (119) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (120) .. (120) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (121) .. (121) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (122) .. (122) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (123) .. (123) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (124) .. (124) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (125) .. (125) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (126) .. (126) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (128) .. (128) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (130) .. (130) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (131) .. (131) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (132) .. (132) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <133> (133) .. (133) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (134) .. (134) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (135) .. (135) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (140) .. (140) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (142) .. (142) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (143) .. (143) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (146) .. (146) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (147) .. (147) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (148) .. (148) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (150) .. (150) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (152) .. (152) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (154) .. (154) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (157) .. (157) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (161) .. (161) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (162) .. (162) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (164). (164) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <166> (166) .. (166) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <168> (168) .. (168) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (172). (172) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (173) .. (173) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE 222 (177) .. (177) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (179) .. (179) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE 222 (185) .. (185) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (188) (188) .. (188) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (191) .. (191) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (194) (194) .. (194) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (195) .. (195) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (196) (196) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (197) .. (197) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (199). (199) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (203) .. (203) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (208) (208) .. (208) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (210) .. (210) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <211> (211) .. (211) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (212) .. (212) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (214) .. (214) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (215) .. (215) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (216) .. (216) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (220) .. (220) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (222) .. (222) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (224) (224) .. (224) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (225) .. (225) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (226) (226) .. (226) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (228) (228) .. (228) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (229) .. (229) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (233) .. (233) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (236) .. (236) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (238) .. (238) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (240) .. (240) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (241) .. (241) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (242) .. (242) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (243) .. (243) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <244> (244) .. (244) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <245> (245) .. (245) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (247) (247) .. (247) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (249) .. (249) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (250) .. (250) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <252> (252) .. (252) <223> Xaa equals any of the naturally occurring L-amino acids <400> 300Cys Ser Ser Gly Gly Gly Gly Val Xaa Ala Asp Ile Gly Xaa Gly Leu1 5 10 15Ala Asp Ala Leu Thr Xaa Pro Xaa Asp Xaa Lys Asp Lys Xaa Leu Xaa            20 25 30Ser Leu Thr Leu Xaa Xaa Ser Xaa Xaa Xaa Asn Xaa Xaa Leu Xaa Leu        35 40 45Xaa Ala Gln Gly Ala Glu Lys Thr Xaa Xaa Xaa Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Xaa Ser Arg Phe Asp Phe Xaa Xaa65 70 75 80Xaa Ile Xaa Val Asp Gly Xaa Xaa Ile Thr Leu Xaa Ser Gly Glu Phe                85 90 95Gln Xaa Tyr Lys Gln Xaa His Ser Ala Xaa Xaa Ala Leu Gln Xaa Glu            100 105 110Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Arg Xaa        115 120 125Phe Xaa Xaa Xaa Xaa Xaa Xaa Gly Glu His Thr Xaa Phe Xaa Xaa Leu    130 135 140Pro Xaa Xaa Xaa Ala Xaa Tyr Xaa Gly Xaa Ala Phe Xaa Ser Asp Asp145 150 155 160Xaa Xaa Gly Xaa Leu Xaa Tyr Xaa Ile Asp Phe Xaa Xaa Lys Gln Gly                165 170 175Xaa Gly Xaa Ile Glu His Leu Lys Xaa Pro Glu Xaa Asn Val Xaa Leu            180 185 190Ala Xaa Xaa Xaa Xaa Lys Xaa Asp Glu Lys Xaa His Ala Val Ile Xaa        195 200 205Gly Xaa Xaa Xaa Tyr Xaa Xaa Xaa Glu Lys Gly Xaa Tyr Xaa Leu Xaa    210 215 220Xaa Xaa Gly Xaa Xaa Ala Gln Glu Xaa Ala Gly Xaa Ala Xaa Val Xaa225 230 235 240Xaa Xaa Xaa Xaa Xaa His Xaa Ile Xaa Xaa Ala Xaa Lys Gln                245 250 <210> 301 <211> 254 <212> PRT <213> Neisseria meningitidis <220> <221> MISC_FEATURE (222) (14) .. (14) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (22) .. (22) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (24) .. (24) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (26) .. (26) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (30) .. (30) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (32) .. (32) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (37) .. (37) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (38) .. (38) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (40) .. (40) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (41) .. (41) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (42) .. (42) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (44) .. (44) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (45) .. (45) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (47) .. (47) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (49) .. (49) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (57) .. (57) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (58) .. (58) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (59) .. (59) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (73) .. (73) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (79) .. (79) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (80) .. (80) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (81) .. (81) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (83) .. (83) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (88) .. (88) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (92) .. (92) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (102) .. (102) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (146) .. (146) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (161) .. (161) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (162) .. (162) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (164). (164) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <166> (166) .. (166) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <168> (168) .. (168) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (172). (172) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (173) .. (173) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE 222 (177) .. (177) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (179) .. (179) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (194) (194) .. (194) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (215) .. (215) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (226) (226) .. (226) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (236) .. (236) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (242) .. (242) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (249) .. (249) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <252> (252) .. (252) <223> Xaa equals any of the naturally occurring L-amino acids <400> 301Cys Ser Ser Gly Gly Gly Gly Val Ala Ala Asp Ile Gly Xaa Gly Leu1 5 10 15Ala Asp Ala Leu Thr Xaa Pro Xaa Asp Xaa Lys Asp Lys Xaa Leu Xaa            20 25 30Ser Leu Thr Leu Xaa Xaa Ser Xaa Xaa Xaa Asn Xaa Xaa Leu Xaa Leu        35 40 45Xaa Ala Gln Gly Ala Glu Lys Thr Xaa Xaa Xaa Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Xaa Ser Arg Phe Asp Phe Xaa Xaa65 70 75 80Xaa Ile Xaa Val Asp Gly Gln Xaa Ile Thr Leu Xaa Ser Gly Glu Phe                85 90 95Gln Ile Tyr Lys Gln Xaa His Ser Ala Val Val Ala Leu Gln Ile Glu            100 105 110Lys Ile Asn Asn Pro Asp Lys Ile Asp Ser Leu Ile Asn Gln Arg Ser        115 120 125Phe Leu Val Ser Gly Leu Gly Gly Glu His Thr Ala Phe Asn Gln Leu    130 135 140Pro Xaa Gly Lys Ala Glu Tyr His Gly Lys Ala Phe Ser Ser Asp Asp145 150 155 160Xaa Xaa Gly Xaa Leu Xaa Tyr Xaa Ile Asp Phe Xaa Xaa Lys Gln Gly                165 170 175Xaa Gly Xaa Ile Glu His Leu Lys Thr Pro Glu Gln Asn Val Glu Leu            180 185 190Ala Xaa Ala Glu Leu Lys Ala Asp Glu Lys Ser His Ala Val Ile Leu        195 200 205Gly Asp Thr Arg Tyr Gly Xaa Glu Glu Lys Gly Thr Tyr His Leu Ala    210 215 220Leu Xaa Gly Asp Arg Ala Gln Glu Ile Ala Gly Xaa Ala Thr Val Lys225 230 235 240Ile Xaa Glu Lys Val His Glu Ile Xaa Ile Ala Xaa Lys Gln                245 250 <210> 302 <211> 255 <212> PRT <213> Neisseria meningitidis <220> <221> MISC_FEATURE (222) (9) .. (9) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (14) .. (14) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (30) .. (30) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (32) .. (32) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (37) .. (37) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (38) .. (38) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (40) .. (40) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (41) .. (41) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (42) .. (42) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (44) .. (44) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (45) .. (45) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (47) .. (47) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (49) .. (49) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (87) .. (87) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (114) .. (114) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <117> (117) .. (117) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (119) .. (119) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (121) .. (121) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (128) .. (128) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (130) .. (130) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE <222> (147) .. (147) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (148) .. (148) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE 222 (149) .. (149) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (192) .. (192) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (195) .. (195) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (196) (196) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (204) (204) .. (204) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (229) .. (229) <223> Xaa equals any of the naturally occurring L-amino acids <220> <221> MISC_FEATURE (222) (230) .. (230) <223> Xaa equals any of the naturally occurring L-amino acids <400> 302Cys Ser Ser Gly Gly Gly Gly Val Xaa Ala Asp Ile Gly Xaa Gly Leu1 5 10 15Ala Asp Ala Leu Thr Ala Pro Leu Asp His Lys Asp Lys Xaa Leu Xaa            20 25 30Ser Leu Thr Leu Xaa Xaa Ser Xaa Xaa Xaa Asn Xaa Xaa Leu Xaa Leu        35 40 45Xaa Ala Gln Gly Ala Glu Lys Thr Tyr Gly Asn Gly Asp Ser Leu Asn    50 55 60Thr Gly Lys Leu Lys Asn Asp Lys Val Ser Arg Phe Asp Phe Ile Arg65 70 75 80Gln Ile Glu Val Asp Gly Xaa Leu Ile Thr Leu Glu Ser Gly Glu Phe                85 90 95Gln Val Tyr Lys Gln Ser His Ser Ala Leu Thr Ala Leu Gln Thr Glu            100 105 110Gln Xaa Gln Asp Xaa Glu Xaa Ser Xaa Lys Met Val Ala Lys Arg Xaa        115 120 125Phe Xaa Ile Gly Asp Ile Ala Gly Glu His Thr Ser Phe Asp Lys Leu    130 135 140Pro Lys Xaa Xaa Xaa Ala Thr Tyr Arg Gly Thr Ala Phe Gly Ser Asp145 150 155 160Asp Ala Gly Gly Lys Leu Thr Tyr Thr Ile Asp Phe Ala Ala Lys Gln                165 170 175Gly His Gly Lys Ile Glu His Leu Lys Ser Pro Glu Leu Asn Val Xaa            180 185 190Leu Ala Xaa Xaa Tyr Ile Lys Pro Asp Glu Lys Xaa His Ala Val Ile        195 200 205Ser Gly Ser Val Leu Tyr Asn Gln Asp Glu Lys Gly Ser Tyr Ser Leu    210 215 220Gly Ile Phe Gly Xaa Xaa Ala Gln Glu Val Ala Gly Ser Ala Glu Val225 230 235 240Glu Thr Ala Asn Gly Ile His His Ile Gly Leu Ala Ala Lys Gln                245 250 255 <210> 303 <211> 31 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 303gcgcggatcc ttactgcttg gcggcaagac c 31 <210> 304 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 304ctattctgca tatgactagg agc 23 <210> 305 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 305agcagcggag gcggcggtgt c 21 <210> 306 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 306tgccgatgca ctaaccgcac c 21 <210> 307 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 307cgtttcgcaa ccatcttccc g 21 <210> 308 <211> 44 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 308gagatctcac tcactcatta ctgcttggcg gcaagaccga tatg 44 <210> 309 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 309gcggatccag cggagggggt ggtgtcgcc 29 <210> 310 <211> 35 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 310gcgcatgctt actgcttggc ggcaagaccg atatg 35 <210> 311 <211> 26 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 311gcggatccag cggaggcggc ggaagc 26 <210> 312 <211> 65 <212> DNA <213> Artificial Sequence <220> <223> Primer <220> <221> misc_feature <222> (46) .. (46) <223> "Y" equals C or T <220> <221> misc_feature (222) (49) .. (49) <223> "W" equals A or T <400> 312gcgcagatct catatgagca gcggaggggg tggtgtcgcc gccgayatwg gtgcggggct 60tgccg 65 <210> 313 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 313ctattctgcg tatgactag 19 <210> 314 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 314gtccgaacgg taaattatcg tg 22 <210> 315 <211> 29 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 315gcggatccag cggaggcggc ggtgtcgcc 29 <210> 316 <211> 34 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 316gagatctcat atgagcagcg gaggcggcgg aagc 34 <210> 317 <211> 16 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 317gacagcctga taaacc 16 <210> 318 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 318gatgccgatt tcgtgaacc 19 <210> 319 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 319gcgcatgcct actgtttgcc ggcgatg 27 <210> 320 <211> 44 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 320gagatctcac tcactcacta ctgtttgccg gcgatgccga tttc 44 <210> 321 <211> 70 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 321gcgcagatct catatgagca gcggaggcgg cggaagcgga ggcggcggtg tcaccgccga 60cataggcacg 70 <210> 322 <211> 59 <212> DNA <213> Artificial Sequence <220> <223> Leader <400> 322atgaaaacaa cgttaaaaat gaccgcactt gcggctcttt ctgcttttgt tttagctgg 59 <210> 323 <211> 75 <212> DNA <213> Artificial Sequence <220> <223> Leader <400> 323atgactagga gcaaacctgt gaaccgaact gccttctgct gcctttccct gaccgccgcc 60ctgattctga ccgcc 75 <210> 324 <211> 75 <212> DNA <213> Artificial Sequence <220> <223> Leader <400> 324atgactagga gcaaacctgt gaaccgaact gccttctgct gcttttctct gaccgccgcc 60ctgattctga ccgcc 75 <210> 325 <211> 75 <212> DNA <213> Artificial Sequence <220> <223> Leader <400> 325atgactagga gcaaacctgt gaaccgaact accttctgtt gcctttctct gaccgccgcc 60ctgattctga ccgcc 75 <210> 326 <211> 75 <212> DNA <213> Artificial Sequence <220> <223> Leader <400> 326atgactagga gtaaacctgt gaatcgaact gccttctgct gcctttctct gaccactgcc 60ctgattctga ccgcc 75 <210> 327 <211> 335 <212> PRT <213> Neisseria meningitidis <400> 327Cys Ser Pro Ala Ala Asp Ser Asn His Pro Ser Gly Gln Asn Ala Pro1 5 10 15Ala Asn Thr Glu Ser Asp Gly Lys Asn Ile Thr Leu Leu Asn Ala Ser            20 25 30Tyr Asp Val Ala Arg Asp Phe Tyr Lys Glu Tyr Asn Pro Leu Phe Ile        35 40 45Lys Thr Tyr Gln Ser Glu His Pro Gly Thr Ser Val Ser Ile Gln Gln    50 55 60Ser His Gly Gly Ser Ser Lys Gln Ala Leu Ser Val Ala Asn Gly Leu65 70 75 80Gln Ala Asp Val Val Thr Met Asn Gln Ser Ser Asp Ile Asp Leu Leu                85 90 95Glu Lys Lys Gly Leu Val Glu Lys Gly Trp Gln Gln Ala Leu Pro Asp            100 105 110His Ala Ala Pro Tyr Thr Ser Thr Met Val Phe Leu Val Arg Lys Asn        115 120 125Asn Pro Lys Gln Ile Arg Asp Trp Asn Asp Leu Ala Lys Asp Gly Val    130 135 140Asn Ile Val Ile Ala Asn Pro Lys Thr Ser Gly Asn Gly Arg Tyr Ala145 150 155 160Phe Leu Gly Ala Tyr Gly Tyr Gly Leu Lys Thr Thr Asn Gly Asn Glu                165 170 175Gln Glu Ala Gln Lys Leu Val Ala Ser Ile Leu Lys Asn Thr Pro Val            180 185 190Phe Glu Asn Gly Gly Arg Ala Ala Thr Thr Thr Phe Thr Gln Arg Asn        195 200 205Ile Gly Asp Val Leu Ile Thr Phe Glu Asn Glu Ala Asn Tyr Val Ser    210 215 220Lys Lys Leu Thr Gln Gly Gln Phe Glu Ile Val Tyr Pro Ser Tyr Thr225 230 235 240Ile Ser Ala Glu Ser Pro Val Ala Val Val Asn Ser Val Val Ala Lys                245 250 255Lys Gly Thr Gln Lys Thr Ala Arg Ala Tyr Leu Glu Tyr Leu Trp Ser            260 265 270Glu Pro Ala Gln Glu Leu Ala Ala Ser Leu Tyr Leu Arg Pro Arg Asn        275 280 285Pro Glu Val Leu Ala Arg His Lys Ala Asp Phe Pro Asp Leu Asp Thr    290 295 300Phe Ser Pro Glu Glu Lys Phe Gly Gly Trp Asp Asn Ile Met Lys Thr305 310 315 320Tyr Phe Ala Asp Gly Gly Ile Phe Asp Arg Leu Thr Ala Gln Lys                325 330 335 <210> 328 <211> 68 <212> PRT <213> Neisseria meningitidis <400> 328Cys Ala Gly Thr Trp Glu Gly Ala Lys Gln Asp Thr Ala Arg Asn Leu1 5 10 15Asp Lys Thr Gln Ala Ala Ala Glu Arg Ala Ala Glu Gln Thr Gly Asn            20 25 30Ala Val Glu Lys Gly Trp Asp Lys Thr Lys Glu Ala Val Lys Lys Gly        35 40 45Gly Asn Ala Val Gly Arg Gly Ile Ser His Leu Gly Gly Lys Ile Glu    50 55 60Asn Ala Thr Glu65 <210> 329 <211> 21 <212> PRT <213> Neisseria meningitidis <400> 329Cys Met Lys Thr Thr Leu Lys Met Thr Ala Leu Ala Ala Leu Ser Ala1 5 10 15Phe Val Leu Ala Gly            20

权利要求:
Claims (342)
[1" claim-type="Currently amended] (a) one encoded by an open reading frame of Neisseria species (ORF2086) encoding a cross-reactive immunogenic antigen that provides immunogenicity against infection by Neisseria meningitidis serogroup B in a subject Above proteins; or
(b) at least one immunogenic portion of at least one protein described in (a); or
(c) at least one biological equivalent of at least one protein described in (a) or an immunogenic fragment described in (b)
Composition comprising a.
[2" claim-type="Currently amended] The composition of claim 1, wherein the one or more proteins comprise the amino acid sequence of any one of SEQ ID NOs: 254 to 259.
[3" claim-type="Currently amended] The method of claim 1, wherein the one or more proteins are Neisseria strains L3 6275, CDC2369, CDC1034, L4 891, B16B6, W135 (ATCC35559), C11, Y (ATCC35561), M98 250732, M98 250771, CDC1135, M97 252153, CDC1610, CDC1492, L8 M978; The composition is encoded by ORF2086 at M97 252988, M97 252697, 6557, 2996, M97 252976, M97 251854, CDC1521, M98 250622, 870446, M97 253248, M98 250809, L5 M981, NMB or M98 250572.
[4" claim-type="Currently amended] The composition of claim 1, wherein the one or more proteins comprise any of the amino acid sequences of SEQ ID NOs: 260-278 or 279-299.
[5" claim-type="Currently amended] The composition of claim 1, wherein the one or more proteins are encoded by ORF2086 in Neisseria strains 880049, M982, CDC1573, M97 253524, or M98 250670.
[6" claim-type="Currently amended] The composition of claim 1, wherein the one or more proteins comprise an amino acid sequence of any one of even numbers SEQ ID NOs: 2-174.
[7" claim-type="Currently amended] The composition of claim 6, further comprising one or more proteins comprising the amino acid sequence of any of the even-numbered sequences 176-252.
[8" claim-type="Currently amended] The composition of claim 1, wherein the one or more proteins comprise the amino acid sequence of any one of even-numbered sequences 224 to 252.
[9" claim-type="Currently amended] The composition of claim 1, wherein the one or more proteins, immunogenic moieties, or biological equivalents are non-pathogenic and substantially free of any infectious impurities.
[10" claim-type="Currently amended] The composition of claim 1, wherein the molecular weight of the one or more proteins measured by mass spectrometry is from about 26,000 to about 30,000 Daltons.
[11" claim-type="Currently amended] The composition of claim 10, wherein the molecular weight of the one or more proteins measured on a 10% to 20% SDS polyacrylamide gel is about 28 to 35 kDa.
[12" claim-type="Currently amended] The composition of claim 1 further comprising a pharmaceutically acceptable buffer, diluent, adjuvant or carrier.
[13" claim-type="Currently amended] The composition of claim 1 further comprising a carrier.
[14" claim-type="Currently amended] The composition of claim 1 further comprising an adjuvant.
[15" claim-type="Currently amended] The composition of claim 14, wherein the adjuvant comprises a liquid.
[16" claim-type="Currently amended] The composition of claim 1, wherein the protein is a recombinant protein.
[17" claim-type="Currently amended] The composition of claim 1, wherein the protein is isolated from native Neisseria species.
[18" claim-type="Currently amended] The composition of claim 1, wherein the protein is lipoprotein.
[19" claim-type="Currently amended] The composition of claim 1, wherein the protein is non-lipidized.
[20" claim-type="Currently amended] The composition of claim 1, further comprising at least one PorA, PorB, transferrin binding protein, or opaque protein (Opc).
[21" claim-type="Currently amended] The composition of claim 1, wherein the composition further comprises one or more additional surface antigens of Neisseria species, wherein the additional surface antigens are non-ORF2086 proteins.
[22" claim-type="Currently amended] The composition of claim 1 further comprising a polysaccharide.
[23" claim-type="Currently amended] The composition of claim 1 comprising additional peptides, polypeptides or proteins and forming a conjugate that induces an immune response against two or more bacteria in a mammal.
[24" claim-type="Currently amended] A composition comprising one or more immunogenic proteins or polypeptides comprising any one of SEQ ID NOs: 254 to 259.
[25" claim-type="Currently amended] The composition of claim 24, wherein the molecular weight of the one or more proteins measured by mass spectrometry is from about 26,000 to about 30,000 Daltons.
[26" claim-type="Currently amended] The composition of claim 25, wherein the molecular weight of the one or more proteins measured on a 10% to 20% SDS polyacrylamide gel is about 28 to 35 kDa.
[27" claim-type="Currently amended] The composition of claim 24 further comprising a pharmaceutically acceptable buffer, diluent, adjuvant or carrier.
[28" claim-type="Currently amended] The composition of claim 24 further comprising a carrier.
[29" claim-type="Currently amended] The composition of claim 24 further comprising an adjuvant.
[30" claim-type="Currently amended] The composition of claim 29, wherein the adjuvant comprises a liquid.
[31" claim-type="Currently amended] The composition of claim 24, wherein the protein is non-lipidized.
[32" claim-type="Currently amended] The composition of claim 24, wherein the protein is a recombinant protein.
[33" claim-type="Currently amended] The composition of claim 24, wherein the protein or polypeptide is isolated from native Neisseria species.
[34" claim-type="Currently amended] The composition of claim 24, wherein the protein is lipoprotein.
[35" claim-type="Currently amended] The composition of claim 24 further comprising at least one PorA, PorB, transferrin binding protein, or opaque protein (Opc).
[36" claim-type="Currently amended] The composition of claim 24, wherein the composition further comprises one or more additional surface antigens of Neisseria spp., Wherein said additional surface antigens are non-ORF2086 proteins.
[37" claim-type="Currently amended] The composition of claim 24 further comprising a polysaccharide.
[38" claim-type="Currently amended] The composition of claim 24 comprising additional peptides, polypeptides or proteins and forming a conjugate that induces an immune response against two or more bacteria in a mammal.
[39" claim-type="Currently amended] A composition comprising one or more immunogenic proteins or polypeptides comprising any of SEQ ID NOs: 260 to 278.
[40" claim-type="Currently amended] The composition of claim 39 further comprising a pharmaceutically acceptable buffer, diluent, adjuvant or carrier.
[41" claim-type="Currently amended] A composition comprising one or more immunogenic proteins or polypeptides comprising any one of SEQ ID NOs: 279 to 299.
[42" claim-type="Currently amended] The composition of claim 41 further comprising a pharmaceutically acceptable buffer, diluent, adjuvant or carrier.
[43" claim-type="Currently amended] x is any amino acid;
The region from amino acid position 5 to amino acid position 9 is any 0 to 5 amino acids;
The region from amino acid position 67 to amino acid position 69 is any 0 to 3 amino acids;
Amino acid position 156 is any 0 to 1 amino acid
A composition comprising one or more isolated proteins comprising the amino acid sequence of SEQ ID NO: 300.
[44" claim-type="Currently amended] The composition of claim 43, wherein the region from amino acid position 5 to amino acid position 9 comprises 0, 4 or 5 amino acids.
[45" claim-type="Currently amended] The composition of claim 43, wherein the region from amino acid position 67 to amino acid position 69 comprises zero or three amino acids.
[46" claim-type="Currently amended] The composition of claim 43, wherein the molecular weight of the one or more proteins measured by mass spectrometry is from about 26,000 to about 30,000 Daltons.
[47" claim-type="Currently amended] The composition of claim 46, wherein the molecular weight of the one or more proteins measured on a 10% to 20% SDS polyacrylamide gel is about 28 to 35 kDa.
[48" claim-type="Currently amended] 44. The composition of claim 43, further comprising a pharmaceutically acceptable buffer, diluent, adjuvant or carrier.
[49" claim-type="Currently amended] 44. The composition of claim 43, further comprising a carrier.
[50" claim-type="Currently amended] 44. The composition of claim 43, further comprising an adjuvant.
[51" claim-type="Currently amended] 51. The composition of claim 50, wherein the adjuvant comprises a liquid.
[52" claim-type="Currently amended] The composition of claim 43, wherein the protein is non-lipidized.
[53" claim-type="Currently amended] The composition of claim 43, wherein the protein is a recombinant protein.
[54" claim-type="Currently amended] The composition of claim 43, wherein the protein is isolated from native Neisseria species.
[55" claim-type="Currently amended] 44. The composition of claim 43, wherein the protein is lipoprotein.
[56" claim-type="Currently amended] The composition of claim 43, further comprising at least one PorA, PorB, transferrin binding protein, or opaque protein (Opc).
[57" claim-type="Currently amended] The composition of claim 43, wherein the composition further comprises one or more additional surface antigens of Neisseria spp., Wherein said additional surface antigens are non-ORF2086 proteins.
[58" claim-type="Currently amended] 44. The composition of claim 43, further comprising a polysaccharide.
[59" claim-type="Currently amended] The composition of claim 43 comprising additional peptides, polypeptides or proteins and forming a conjugate that induces an immune response against two or more bacteria in a mammal.
[60" claim-type="Currently amended] (a) one or more proteins comprising the amino acid sequence of any of the even numbered sequences 2 to 252;
(b) one or more proteins encoded by a polynucleotide that hybridizes to a polynucleotide comprising the nucleic acid sequence of any of SEQ ID NOS: 1-253 under stringent conditions;
(c) at least one immunogenic portion of at least one protein described in (a) or (b); or
(d) at least one biological equivalent of at least one protein described in (a) or (b) or an immunogenic fragment described in (c)
Composition comprising a.
[61" claim-type="Currently amended] 61. The composition of claim 60, wherein the one or more proteins comprise the amino acid sequence of any of SEQ ID NOs: 2 to 174.
[62" claim-type="Currently amended] 62. The composition of claim 61, further comprising one or more proteins comprising the amino acid sequence of any of the even-numbered sequences 176-252.
[63" claim-type="Currently amended] 61. The composition of claim 60, wherein the one or more proteins comprise the amino acid sequence of any one of even numbers SEQ ID NOs: 2-12.
[64" claim-type="Currently amended] 61. The composition of claim 60, wherein the one or more proteins comprise the amino acid sequence of any of SEQ ID NOs: 14-24.
[65" claim-type="Currently amended] 61. The composition of claim 60, wherein the one or more proteins comprise the amino acid sequence of any of SEQ ID NOs: 26 to 42.
[66" claim-type="Currently amended] 61. The composition of claim 60, wherein the one or more proteins comprise the amino acid sequence of any one of even numbers SEQ ID NOs: 50-60.
[67" claim-type="Currently amended] 61. The composition of claim 60, wherein the one or more proteins comprise the amino acid sequence of any of SEQ ID NOs: 62-108.
[68" claim-type="Currently amended] 61. The composition of claim 60, wherein the one or more proteins comprise the amino acid sequence of any of SEQ ID NOs: 110-138.
[69" claim-type="Currently amended] 61. The composition of claim 60, wherein the one or more proteins comprise an amino acid sequence of any of SEQ ID NOs: 140 to 156.
[70" claim-type="Currently amended] 61. The composition of claim 60, wherein the one or more proteins comprise the amino acid sequence of any of the even-numbered sequences 158-174.
[71" claim-type="Currently amended] 61. The composition of claim 60, wherein the one or more proteins comprise the amino acid sequence of any of the even-numbered sequences 224 to 252.
[72" claim-type="Currently amended] 61. The composition of claim 60, further comprising at least one PorA, PorB, transferrin binding protein, or opaque protein (Opc).
[73" claim-type="Currently amended] 61. The composition of claim 60, wherein the composition further comprises one or more additional surface antigens of Neisseria spp., Wherein said additional surface antigens are non-ORF2086 proteins.
[74" claim-type="Currently amended] 61. The composition of claim 60, wherein the molecular weight of the one or more proteins measured by mass spectrometry is from about 26,000 to about 30,000 Daltons.
[75" claim-type="Currently amended] The composition of claim 74, wherein the molecular weight of the one or more proteins measured on a 10% to 20% SDS polyacrylamide gel is about 28 to 35 kDa.
[76" claim-type="Currently amended] 61. The composition of claim 60, further comprising a pharmaceutically acceptable buffer, diluent, adjuvant or carrier.
[77" claim-type="Currently amended] 61. The composition of claim 60, further comprising a carrier.
[78" claim-type="Currently amended] 61. The composition of claim 60, further comprising an adjuvant.
[79" claim-type="Currently amended] 79. The composition of claim 78, wherein the adjuvant comprises a liquid.
[80" claim-type="Currently amended] 61. The composition of claim 60, wherein the protein is non-lipidized.
[81" claim-type="Currently amended] 61. The composition of claim 60, wherein the protein is a recombinant protein.
[82" claim-type="Currently amended] 61. The composition of claim 60, wherein the protein is isolated from native Neisseria species.
[83" claim-type="Currently amended] 61. The composition of claim 60, wherein the protein is lipoprotein.
[84" claim-type="Currently amended] 61. The composition of claim 60, further comprising a polysaccharide.
[85" claim-type="Currently amended] 61. The composition of claim 60, comprising additional peptides, polypeptides or proteins and forming a conjugate that induces an immune response against two or more bacteria in a mammal.
[86" claim-type="Currently amended] A composition comprising one or more antigens of a first bacterial strain of Neisseria spp., Providing immunogenicity to a subject's infection by a second bacterial strain of Neisseria spp.
[87" claim-type="Currently amended] 87. The composition of claim 86, wherein the first strain is a strain of Neisseria species and the second strain is a strain of Neisseria meningitidis serogroup B.
[88" claim-type="Currently amended] The method of claim 86, wherein the first strain is strain L3 6275, CDC2369, CDC1034, L4 891, B16B6, W135 (ATCC35559), C11, Y (ATCC35561), M98 250732, M98 250771, CDC1135, M97 252153, CDC1610, CDC1492, L8 M978; M97 252988, M97 252697, 6557, 2996, M97 252976, M97 251854, CDC1521, M98 250622, 870446, M97 253248, M98 250809, L5 M981, NMB or M98 250572.
[89" claim-type="Currently amended] The composition of claim 86, wherein the first strain is strain 880049, M982, CDC1573, M97 253524, or M98 250670.
[90" claim-type="Currently amended] 87. The composition of claim 86, wherein the protein is a recombinant protein.
[91" claim-type="Currently amended] 87. The composition of claim 86, wherein the protein is isolated from native Neisseria species.
[92" claim-type="Currently amended] 87. The composition of claim 86, wherein the protein is lipoprotein.
[93" claim-type="Currently amended] 87. The composition of claim 86, further comprising a pharmaceutically acceptable buffer, diluent, adjuvant or carrier.
[94" claim-type="Currently amended] 87. The composition of claim 86, further comprising a carrier.
[95" claim-type="Currently amended] 87. The composition of claim 86, further comprising an adjuvant.
[96" claim-type="Currently amended] 97. The composition of claim 95, wherein the adjuvant comprises a liquid.
[97" claim-type="Currently amended] 87. The composition of claim 86, wherein the protein is non-lipidized.
[98" claim-type="Currently amended] 87. The composition of claim 86, further comprising a polysaccharide.
[99" claim-type="Currently amended] 87. The composition of claim 86, comprising additional peptides, polypeptides or proteins and forming a conjugate that induces an immune response against two or more pathogens in a mammal.
[100" claim-type="Currently amended] x is any amino acid;
The region from amino acid position 5 to amino acid position 8 is any 0 to 4 amino acids;
The region from amino acid position 66 to amino acid position 68 is any 0 to 3 amino acids
A composition comprising one or more isolated proteins comprising the amino acids of SEQ ID NO: 301.
[101" claim-type="Currently amended] 101. The composition of claim 100, wherein the molecular weight of the one or more proteins measured by mass spectrometry is about 26,000 to about 30,000 Daltons.
[102" claim-type="Currently amended] 102. The composition of claim 101, wherein the molecular weight of at least one protein measured on a 10% to 20% SDS polyacrylamide gel is about 28 to 35 kDa.
[103" claim-type="Currently amended] 101. The composition of claim 100, further comprising a pharmaceutically acceptable buffer, diluent, adjuvant or carrier.
[104" claim-type="Currently amended] 101. The composition of claim 100, further comprising a carrier.
[105" claim-type="Currently amended] 101. The composition of claim 100, further comprising an adjuvant.
[106" claim-type="Currently amended] 107. The composition of claim 105, wherein the adjuvant comprises a liquid.
[107" claim-type="Currently amended] 101. The composition of claim 100, wherein the protein is non-lipidized.
[108" claim-type="Currently amended] 101. The composition of claim 100, wherein the protein is a recombinant protein.
[109" claim-type="Currently amended] 101. The composition of claim 100, wherein the protein is isolated from native Neisseria species.
[110" claim-type="Currently amended] 101. The composition of claim 100, wherein the protein is lipoprotein.
[111" claim-type="Currently amended] 101. The composition of claim 100, further comprising a polysaccharide.
[112" claim-type="Currently amended] 101. The composition of claim 100, comprising additional peptides, polypeptides or proteins and forming an immune response against two or more bacteria in a mammal.
[113" claim-type="Currently amended] 101. The composition of claim 100, wherein the region from amino acid position 5 to amino acid position 8 comprises zero or four amino acids.
[114" claim-type="Currently amended] 101. The composition of claim 100, wherein the region from amino acid position 66 to amino acid position 68 comprises zero or three amino acids.
[115" claim-type="Currently amended] x is any amino acid;
The region of amino acid position 8 to amino acid position 12 is any 0-5 amino acid
A composition comprising one or more isolated proteins comprising the amino acid sequence of SEQ ID NO: 302.
[116" claim-type="Currently amended] 116. The composition of claim 115, wherein the region of amino acid position 8 to amino acid position 12 comprises zero or five amino acids.
[117" claim-type="Currently amended] 116. The composition of claim 115, wherein the molecular weight of the one or more proteins measured by mass spectrometry is about 26,000 to about 30,000 Daltons.
[118" claim-type="Currently amended] 118. The composition of claim 117, wherein the molecular weight of at least one protein measured on a 10% to 20% SDS polyacrylamide gel is about 28 to 35 kDa.
[119" claim-type="Currently amended] 116. The composition of claim 115, further comprising a pharmaceutically acceptable buffer, diluent, adjuvant or carrier.
[120" claim-type="Currently amended] 116. The composition of claim 115, further comprising a carrier.
[121" claim-type="Currently amended] 116. The composition of claim 115, further comprising an adjuvant.
[122" claim-type="Currently amended] 121. The composition of claim 121, wherein the adjuvant comprises a liquid.
[123" claim-type="Currently amended] 116. The composition of claim 115, wherein the protein is non-lipidized.
[124" claim-type="Currently amended] 116. The composition of claim 115, wherein the protein is a recombinant polypeptide.
[125" claim-type="Currently amended] 116. The composition of claim 115, wherein the protein is isolated from a natural source.
[126" claim-type="Currently amended] 116. The composition of claim 115, further comprising a polysaccharide.
[127" claim-type="Currently amended] 116. The composition of claim 115, wherein the composition comprises additional peptides, polypeptides or proteins and forms an immune response against two or more bacteria in a mammal.
[128" claim-type="Currently amended] (a) one or more proteins encoded by an open reading frame of Neisseria species (ORF2086) encoding a cross-reactive immunogenic antigen that provides immunogenicity against infection by Neisseria meningitidis serogroup B in a subject; or
(b) at least one immunogenic portion of at least one protein described in (a); or
(c) one or more biological equivalents of one or more proteins described in (a) or one immunogenic fragment described in (b)
A composition comprising one or more antibodies that immunospecifically bind to any of them.
[129" claim-type="Currently amended] 129. The composition of claim 128, wherein the antibody is a monoclonal antibody.
[130" claim-type="Currently amended] 129. The composition of claim 128, further comprising a pharmaceutically acceptable carrier.
[131" claim-type="Currently amended] (a) one or more proteins comprising any of SEQ ID NOs: 254 to 259; or
(b) at least one immunogenic portion of at least one protein described in (a); or
(c) one or more biological equivalents of one or more proteins described in (a) or one immunogenic fragment described in (b)
A composition comprising one or more antibodies that immunospecifically bind to any of them.
[132" claim-type="Currently amended] 131. The composition of claim 131, wherein the one or more proteins, immunogenic portions thereof or biological equivalents thereof comprises any of SEQ ID NOs: 260 to 299.
[133" claim-type="Currently amended] 131. The composition of claim 131, wherein the one or more antibodies is a monoclonal antibody.
[134" claim-type="Currently amended] x is any amino acid;
The region of amino acid position 5 to amino acid position 9 is any 0 to 5 amino acids;
The region of amino acid position 67 to amino acid position 69 is any 0 to 3 amino acids;
Amino acid position 156 is any 0 to 1 amino acid
A composition comprising one or more antibodies immunospecifically binding to one or more isolated proteins comprising the amino acid sequence of SEQ ID NO: 300.
[135" claim-type="Currently amended] 134. The composition of claim 134, wherein the one or more antibodies is a monoclonal antibody.
[136" claim-type="Currently amended] (a) one or more proteins comprising the amino acid sequence of any of the even numbered sequences 2 to 252; or
(b) one or more proteins encoded by a polynucleotide that hybridizes to a polynucleotide comprising the nucleic acid sequence of any of SEQ ID NOS: 1-253 under stringent conditions;
(c) at least one immunogenic portion of at least one protein described in (a) or (b); or
(d) at least one biological equivalent of at least one protein described in (a) or (b) or an immunogenic fragment described in (c)
A composition comprising one or more antibodies that immunospecifically bind to any of them.
[137" claim-type="Currently amended] (a) one or more proteins encoded by an open reading frame of Neisseria species (ORF2086) encoding a cross-reactive immunogenic antigen that provides immunogenicity against infection by Neisseria meningitidis serogroup B in a subject, or Encoding one or more immunogenic portions or biological equivalents of said one or more proteins; or
(b) hybridize to any of the polynucleotides described in (a) under stringent conditions
A composition comprising one or more polynucleotides.
[138" claim-type="Currently amended] 137. The composition of claim 137, further comprising a P4 leader sequence (SEQ ID NO: 322).
[139" claim-type="Currently amended] 138. The composition of claim 137 comprising a vector.
[140" claim-type="Currently amended] 139. The composition of claim 139, wherein the vector is a plasmid.
[141" claim-type="Currently amended] 141. The composition of claim 139, wherein the vector is a phage.
[142" claim-type="Currently amended] 138. The composition of claim 137, wherein the stringent conditions are highly stringent southern hybridization conditions.
[143" claim-type="Currently amended] 137. The composition of claim 137, further comprising a P4 leader sequence (SEQ ID NO: 322).
[144" claim-type="Currently amended] 137. The composition of claim 137, wherein the polynucleotide is a recombinant polynucleotide.
[145" claim-type="Currently amended] 138. The composition of claim 137, wherein the polynucleotide is isolated from a natural source.
[146" claim-type="Currently amended] 137. The composition of claim 137, further comprising a nucleic acid sequence encoding additional peptides, polypeptides or proteins.
[147" claim-type="Currently amended] (a) encodes one or more isolated proteins comprising any of SEQ ID NOs: 254 to 259, 260 to 278 or 279 to 299, or
(b) hybridize to any of the polynucleotides described in (a) under stringent conditions
A composition comprising one or more polynucleotides.
[148" claim-type="Currently amended] 147. The composition of claim 147, further comprising a P4 leader sequence (SEQ ID NO: 322).
[149" claim-type="Currently amended] 147. The composition of claim 147, comprising a vector.
[150" claim-type="Currently amended] 147. The composition of claim 147, wherein the stringent conditions are highly stringent southern hybridization conditions.
[151" claim-type="Currently amended] 147. The composition of claim 147, further comprising a P4 leader sequence (SEQ ID NO: 322).
[152" claim-type="Currently amended] 147. The composition of claim 147, wherein the polynucleotide is a recombinant polynucleotide.
[153" claim-type="Currently amended] 147. The composition of claim 147, wherein the polynucleotide is isolated from a natural source.
[154" claim-type="Currently amended] 147. The composition of claim 147, further comprising a nucleic acid sequence encoding additional peptides, polypeptides or proteins.
[155" claim-type="Currently amended] (a) x is any amino acid, the region at amino acid position 5 to amino acid position 9 is any 0 to 5 amino acids, and the region at amino acid position 67 to amino acid position 69 is any 0 to 3 amino acids; Encoding one or more proteins comprising the amino acid sequence of SEQ ID NO: 300 wherein amino acid position 156 is any 0 to 1 amino acid, or
(b) hybridize to any of the polynucleotides described in (a) under stringent conditions
A composition comprising one or more polynucleotides.
[156" claim-type="Currently amended] 155. The composition of claim 155, further comprising a P4 leader sequence (SEQ ID NO: 322).
[157" claim-type="Currently amended] (a) (i) one or more proteins comprising the amino acid sequence of any of the even numbered sequences 2 to 252; (ii) one or more proteins encoded by a polynucleotide that hybridize to a polynucleotide comprising the nucleic acid sequence of any of SEQ ID NOs: 1-253 under stringent conditions; (iii) at least one immunogenic portion of at least one protein described in (i) or (ii); Or (iv) at least one biological equivalent of at least one protein described in (i) or (ii) or an immunogenic fragment described in (iii)
One or more polynucleotides encoding one or more of or
(b) one or more polynucleotides that hybridize to any of the polynucleotides described in (a) under stringent conditions
Composition comprising a.
[158" claim-type="Currently amended] 162. The composition of claim 157, wherein the one or more polynucleotides comprise a nucleic acid sequence of any of the odd numbered sequences 1-253.
[159" claim-type="Currently amended] 162. The composition of claim 157, comprising a vector.
[160" claim-type="Currently amended] 162. The composition of claim 157, wherein the stringent conditions are highly stringent Southern hybridization conditions.
[161" claim-type="Currently amended] 158. The composition of claim 157, further comprising a nucleic acid sequence encoding additional peptides, polypeptides or proteins.
[162" claim-type="Currently amended] (a) one or more polynucleotides encoding one or more antigens of the first bacterial strain of Neisseria spp., providing immunogenicity to a subject's infection by a second bacterial strain of Neisseria spp .; or
(b) one or more polynucleotides that hybridize to one or more polynucleotides of (a) under stringent conditions
Composition comprising a.
[163" claim-type="Currently amended] 162. The composition of claim 162, wherein the one or more isolated polynucleotides comprise a nucleic acid sequence of any of the odd numbered sequences 1-253.
[164" claim-type="Currently amended] 162. The composition of claim 162, further comprising a P4 leader sequence (SEQ ID NO: 322).
[165" claim-type="Currently amended] 162. The composition of claim 162 comprising a vector.
[166" claim-type="Currently amended] 162. The composition of claim 162, wherein the stringent conditions are highly stringent Southern hybridization conditions.
[167" claim-type="Currently amended] 162. The composition of claim 162, further comprising a nucleic acid sequence encoding additional peptides, polypeptides or proteins.
[168" claim-type="Currently amended] (a) one or more proteins comprising the amino acid sequence of any one of SEQ ID NOs: 254 to 259, 260 to 278 or 279 to 299; or
(b) at least one immunogenic portion of at least one protein described in (a); or
(c) at least one biological equivalent of at least one protein described in (a) or an immunogenic fragment described in (b)
A composition comprising a vector comprising any of.
[169" claim-type="Currently amended] 168. The composition of claim 168, wherein the vector is a plasmid.
[170" claim-type="Currently amended] 168. The composition of claim 168, wherein the vector is a phage.
[171" claim-type="Currently amended] 168. The composition of claim 168, wherein the vector is bacteriophage.
[172" claim-type="Currently amended] 168. The composition of claim 168, wherein the vector is moderate phage.
[173" claim-type="Currently amended] x is any amino acid;
The region of amino acid position 5 to amino acid position 9 is any 0 to 5 amino acids;
The region of amino acid position 67 to amino acid position 69 is any 0 to 3 amino acids;
Amino acid position 156 is any 0 to 1 amino acid
A composition comprising a vector comprising one or more polynucleotides encoding a protein comprising the amino acid sequence of SEQ ID NO: 300.
[174" claim-type="Currently amended] 174. The composition of claim 173, wherein the vector is a plasmid.
[175" claim-type="Currently amended] 174. The composition of claim 173, wherein the vector is a phage.
[176" claim-type="Currently amended] (a) one or more polynucleotides encoding one or more polypeptides of even numbers SEQ ID NOs: 2-252; or
(b) one or more polynucleotides that hybridize to one or more polynucleotides of (a) under stringent conditions
A composition comprising a vector comprising any of.
[177" claim-type="Currently amended] 176. The composition of claim 176, wherein the vector comprises the nucleic acid sequence of any one of SEQ ID NOs: 1-153.
[Claim 177] 176. The composition of claim 176, wherein the vector is a plasmid.
[178" claim-type="Currently amended] 176. The composition of claim 176, wherein the vector is a phage.
[179" claim-type="Currently amended] 176. The composition of claim 176, wherein the vector is bacteriophage.
[180" claim-type="Currently amended] 176. The composition of claim 176, wherein the vector is moderate phage.
[181" claim-type="Currently amended] (a) one or more proteins encoded by an open reading frame of Neisseria species (ORF2086) encoding a cross-reactive immunogenic antigen that provides immunogenicity against infection by Neisseria meningitidis serogroup B in a subject; or
(b) at least one immunogenic portion of at least one protein described in (a); or
(c) at least one biological equivalent of at least one protein described in (a) or an immunogenic fragment described in (b)
A composition comprising a host cell transformed / transfected or infected with a vector comprising any of.
[182" claim-type="Currently amended] (a) one or more proteins comprising any of SEQ ID NOs: 254 to 259, 260 to 278 or 279 to 299; or
(b) at least one immunogenic portion of at least one protein described in (a); or
(c) at least one biological equivalent of at least one protein described in (a) or an immunogenic fragment described in (b)
A composition comprising a host cell transformed / transfected or infected with a vector comprising any of.
[183" claim-type="Currently amended] (a) one or more proteins encoded by an open reading frame of Neisseria species (ORF2086) encoding a cross-reactive immunogenic antigen that provides immunogenicity against infection by Neisseria meningitidis serogroup B in a subject; or
(b) at least one immunogenic portion of at least one protein described in (a); or
(c) at least one biological equivalent of at least one protein described in (a) or an immunogenic fragment described in (b)
A composition prepared by a method comprising expressing in a host cell a nucleic acid sequence encoding any of the above.
[184" claim-type="Currently amended] 184. The composition of claim 183, wherein the nucleic acid sequence is any one of odd numbered SEQ ID NOs: 1-253.
[185" claim-type="Currently amended] 184. The composition of claim 183, wherein the nucleic acid sequence encodes a protein comprising any of the even numbered sequences 2 to 252.
[186" claim-type="Currently amended] 184. The composition of claim 183, wherein the nucleic acid sequence encodes a protein comprising any of the even numbered sequences 2-174.
[187" claim-type="Currently amended] 184. The composition of claim 183, wherein the molecular weight of the protein measured by mass spectrometry is from about 26,000 to about 30,000 Daltons.
[188" claim-type="Currently amended] 187. The composition of claim 187, wherein the protein has a molecular weight of about 28 to 35 kDa as measured on a 10% to 20% SDS polyacrylamide gel.
[189" claim-type="Currently amended] 184. The composition of claim 183, further comprising a pharmaceutically acceptable buffer, diluent, adjuvant or carrier.
[190" claim-type="Currently amended] 184. The composition of claim 183, further comprising a carrier.
[191" claim-type="Currently amended] 184. The composition of claim 183, further comprising an adjuvant.
[192" claim-type="Currently amended] 192. The composition of claim 191, wherein the adjuvant is a liquid.
[193" claim-type="Currently amended] 184. The composition of claim 183, wherein the protein is a lipidated protein.
[194" claim-type="Currently amended] (a) one or more proteins encoded by an open reading frame of Neisseria species (ORF2086) encoding a cross-reactive immunogenic antigen that provides immunogenicity against infection by Neisseria meningitidis serogroup B in a subject; or
(b) at least one immunogenic portion of at least one protein described in (a); or
(c) at least one biological equivalent of at least one protein described in (a) or an immunogenic fragment described in (b)
A composition prepared by a method comprising the isolation and purification of any of Neisseria species.
[195" claim-type="Currently amended] 194. The composition of claim 194, wherein the one or more polynucleotides comprises a nucleic acid sequence of any of the odd numbered sequences 1-253.
[196" claim-type="Currently amended] 194. The composition of claim 194, wherein the method further comprises introducing a non-natural leader sequence into one or more isolated polynucleotides.
[197" claim-type="Currently amended] 195. The composition of claim 196, wherein the non-natural leader sequence is a P4 leader sequence (SEQ ID NO: 322).
[198" claim-type="Currently amended] (a) one or more proteins comprising any of SEQ ID NOs: 254 to 259, 260 to 278 or 279 to 299; or
(b) at least one immunogenic portion of at least one protein described in (a); or
(c) at least one biological equivalent of at least one protein described in (a) or an immunogenic fragment described in (b)
A composition prepared by a method comprising the isolation and purification of any of Neisseria species.
[199" claim-type="Currently amended] 199. The composition of claim 198, wherein the molecular weight of the polypeptide is about 26,000 to about 30,000 Daltons, determined by mass spectrometry.
[200" claim-type="Currently amended] 201. The composition of claim 199, wherein the polypeptide has a molecular weight of about 28 to 35 kDa as measured on a 10% to 20% SDS polyacrylamide gel.
[201" claim-type="Currently amended] 199. The composition of claim 198, further comprising a pharmaceutically acceptable buffer, diluent, adjuvant or carrier.
[202" claim-type="Currently amended] 198. The composition of claim 198, further comprising a carrier.
[203" claim-type="Currently amended] 199. The composition of claim 198, further comprising an adjuvant.
[204" claim-type="Currently amended] 203. The composition of claim 203, wherein the adjuvant comprises a liquid.
[205" claim-type="Currently amended] 199. The composition of claim 198, wherein the protein is a lipidated protein.
[206" claim-type="Currently amended] x is any amino acid;
The region of amino acid position 5 to amino acid position 9 is any 0 to 5 amino acids;
The region of amino acid position 67 to amino acid position 69 is any 0 to 3 amino acids;
Amino acid position 156 is any 0 to 1 amino acid
A composition prepared by a method comprising inserting into an vector one or more isolated proteins comprising the amino acid sequence of SEQ ID NO: 300.
[207" claim-type="Currently amended] 206. The composition of claim 206, wherein the vector is a plasmid.
[208" claim-type="Currently amended] 206. The composition of claim 206, wherein the vector is a phage.
[209" claim-type="Currently amended] 206. The composition of claim 206, wherein the vector is bacteriophage.
[210" claim-type="Currently amended] 206. The composition of claim 206, wherein the vector is moderate phage.
[211" claim-type="Currently amended] 206. The composition of claim 206, further comprising a non-natural leader sequence.
[212" claim-type="Currently amended] 213. The composition of claim 211, wherein the non-natural leader sequence is a P4 leader sequence (SEQ ID NO: 322).
[213" claim-type="Currently amended] (a) one or more proteins encoded by an open reading frame of Neisseria species (ORF2086) encoding a cross-reactive immunogenic antigen that provides immunogenicity against infection by Neisseria meningitidis serogroup B in a subject, or One or more isolated polynucleotides encoding one or more immunogenic portions or biological equivalents of said one or more proteins, and
(b) a non-natural leader sequence associated with the one or more isolated polynucleotides
A composition prepared by a method comprising expressing in a host cell.
[214" claim-type="Currently amended] 213. The composition of claim 213, wherein the non-natural leader sequence is a P4 leader sequence (SEQ ID NO: 322).
[215" claim-type="Currently amended] (a) one or more proteins encoded by an open reading frame of Neisseria species (ORF2086) encoding a cross-reactive immunogenic antigen that provides immunogenicity against infection by Neisseria meningitidis serogroup B in a subject; or
(b) at least one immunogenic portion of at least one protein described in (a); or
(c) at least one biological equivalent of at least one protein described in (a) or an immunogenic fragment described in (b)
Expressing a nucleic acid sequence encoding any of them in a host cell; or
Expressing in a host cell a nucleic acid sequence that hybridizes to said nucleic acid sequence under stringent conditions
Composition prepared by the method comprising a.
[216" claim-type="Currently amended] 215. The composition of claim 215, wherein the nucleic acid sequence is any one of odd numbered sequences 1-253.
[217" claim-type="Currently amended] 215. The composition of claim 215, wherein the nucleic acid sequence encodes any of the even numbered sequences 2 to 252.
[218" claim-type="Currently amended] 215. The composition of claim 215, wherein the molecular weight of the protein measured by mass spectrometry is about 26,000 to about 30,000 Daltons.
[219" claim-type="Currently amended] 218. The composition of claim 218, wherein the molecular weight of the protein measured on a 10% to 20% SDS polyacrylamide gel is about 28 to 35 kDa.
[220" claim-type="Currently amended] 215. The composition of claim 215, further comprising a pharmaceutically acceptable buffer, diluent, adjuvant or carrier.
[221" claim-type="Currently amended] 215. The composition of claim 215 further comprising a carrier.
[222" claim-type="Currently amended] 215. The composition of claim 215 further comprising an adjuvant.
[223" claim-type="Currently amended] 222. The composition of claim 222, wherein the adjuvant comprises a liquid.
[224" claim-type="Currently amended] 215. The composition of claim 215, wherein the stringent conditions are highly stringent southern hybridization conditions.
[225" claim-type="Currently amended] (a) one or more polynucleotides encoding one or more polypeptides comprising the amino acids of any of the even numbers SEQ ID NOs: 2-252; or
(b) one or more polynucleotides that hybridize to one or more polynucleotides of (a) under stringent conditions
A composition prepared by a method comprising the isolation and purification of any of Neisseria species.
[226" claim-type="Currently amended] 253. The composition of claim 225, wherein the one or more polynucleotides comprise the nucleic acid sequence of any of the odd numbered sequences 1-253.
[227" claim-type="Currently amended] 253. The composition of claim 225, wherein the method further comprises introducing a non-natural leader sequence into one or more polynucleotides.
[228" claim-type="Currently amended] 227. The composition of claim 227, wherein the non-natural leader sequence is a P4 leader sequence (SEQ ID NO: 322).
[229" claim-type="Currently amended] (a) one or more proteins comprising the amino acid sequence of any of the even numbered sequences 2 to 252;
(b) one or more proteins encoded by a polynucleotide that hybridizes to a polynucleotide comprising the nucleic acid sequence of any of SEQ ID NOS: 1-253 under stringent conditions;
(c) at least one immunogenic portion of at least one protein described in (a) or (b); or
(d) at least one biological equivalent of at least one protein described in (a) or (b) or an immunogenic fragment described in (c)
A composition prepared by a method comprising the isolation and purification of any of Neisseria species.
[230" claim-type="Currently amended] 229. The composition of claim 229, wherein the molecular weight of the protein measured by mass spectrometry is about 26,000 to about 30,000 Daltons.
[231" claim-type="Currently amended] 234. The composition of claim 230, wherein the molecular weight of the protein measured on a 10% to 20% SDS polyacrylamide gel is about 28 to 35 kDa.
[232" claim-type="Currently amended] 231. The composition of claim 229, further comprising a pharmaceutically acceptable buffer, diluent, adjuvant or carrier.
[233" claim-type="Currently amended] 231. The composition of claim 229, further comprising a carrier.
[234" claim-type="Currently amended] 231. The composition of claim 229, further comprising an adjuvant.
[235" claim-type="Currently amended] 234. The composition of claim 234, wherein the adjuvant comprises a liquid.
[236" claim-type="Currently amended] 231. The composition of claim 229, wherein the stringent conditions are highly stringent Southern hybridization conditions.
[237" claim-type="Currently amended] (a) one or more isolated polynucleotides encoding one or more polypeptides comprising any of the even numbered sequences 2 to 252; or
(b) one or more isolated polynucleotides that hybridize to one or more polynucleotides of (a) under stringent conditions
A composition prepared by a method comprising introducing any of the vectors into a vector.
[238" claim-type="Currently amended] 237. The composition of claim 237, wherein the vector is a plasmid.
[239" claim-type="Currently amended] 237. The composition of claim 237, wherein the vector is a phage.
[240" claim-type="Currently amended] 237. The composition of claim 237, wherein the vector is bacteriophage.
[241" claim-type="Currently amended] 237. The composition of claim 237, wherein the vector is moderate phage.
[242" claim-type="Currently amended] 237. The composition of claim 237, further comprising a non-natural leader sequence.
[243" claim-type="Currently amended] 242. The composition of claim 242, wherein the non-natural leader sequence is a P4 leader sequence (SEQ ID NO: 322).
[244" claim-type="Currently amended] (a) one or more proteins encoded by an open reading frame of Neisseria species (ORF2086) encoding a cross-reactive immunogenic antigen that provides immunogenicity against infection by Neisseria meningitidis serogroup B in a subject, or Encoding one or more immunogenic portions or biological equivalents of said one or more proteins; or
(b) hybridize to any of the polynucleotides described in (a) under stringent conditions
A composition prepared by a method comprising expressing at least one polynucleotide in a host cell.
[245" claim-type="Currently amended] 244. The composition of claim 244, further comprising a non-natural leader sequence associated with one or more polynucleotides.
[246" claim-type="Currently amended] 245. The composition of claim 245, wherein the non-natural leader sequence is a P4 leader sequence (SEQ ID NO: 322).
[247" claim-type="Currently amended] A composition comprising at least one immunogenic non-strain specific Neisseria meningitidis antigen, which is nonpathogenic and substantially free of any infectious impurities.
[248" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even numbered sequences 2-6.
[249" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even numbered sequences 8-12.
[250" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even numbered sequences 14-18.
[251" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any one of even-numbered sequences 20 to 24.
[252" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even numbered sequences 26-30.
[253" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any one of even-numbered sequences 32 to 36.
[254" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any one of even-numbered sequences 38 to 42.
[255" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any one of even-numbered sequences 44 to 48.
[256" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of even-numbered sequences 50 to 54.
[257" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even numbered sequences 56 to 60.
[258" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even numbered sequences 62 to 66.
[259" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even numbered sequences 68 to 72.
[260" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even-numbered sequences 74 to 78.
[261" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even numbered sequences 80 to 84.
[262" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any one of even-numbered sequences 86 to 90.
[263" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even numbered sequences 92 to 96.
[264" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even numbers SEQ ID NOs: 98-102.
[265" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even numbered sequences 104 to 108.
[266" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any one of even-numbered sequences 110 to 114.
[267" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any one of even-numbered sequences 116 to 120.
[268" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even-numbered sequences 122-126.
[269" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any one of even-numbered sequences 128 to 132.
[270" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even-numbered sequences 134 to 138.
[271" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any one of even-numbered sequences 140 to 144.
[272" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even-numbered sequences 146 to 150.
[273" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even-numbered sequences 152 to 156.
[274" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even-numbered sequences 158 to 162.
[275" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even-numbered sequences 164 to 168.
[276" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even numbered sequences 170 to 174.
[277" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any one of even-numbered sequences 176 to 180.
[278" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even-numbered sequences 182 to 186.
[279" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any one of even-numbered sequences 188 to 192.
[280" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even-numbered sequences 194-198.
[281" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any one of even-numbered sequences 200 to 204.
[282" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even-numbered sequences 206-210.
[283" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even numbered sequences 212 to 216.
[284" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even-numbered sequences 218-222.
[285" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even-numbered sequences 224 to 228.
[286" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even-numbered sequences 230 to 234.
[287" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any one of even-numbered sequences 236 to 240.
[288" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even-numbered sequences 242 to 246.
[289" claim-type="Currently amended] 247. The antigen of claim 247, wherein the antigen comprises an amino acid sequence having at least about 70% amino acid sequence homology to any of the even numbered sequences 248 to 252.
[290" claim-type="Currently amended] 2. The use of the composition of claim 1 in the manufacture of a medicament for inducing an immune response in a mammal.
[291" claim-type="Currently amended] 290. The use of claim 290, wherein the composition is administered parenterally.
[292" claim-type="Currently amended] 290. The use of claim 290, wherein the composition is administered mucosally.
[293" claim-type="Currently amended] 2. Use of a composition of claim 1 in a medicament effective against bacterial meningitis in a mammal.
[294" claim-type="Currently amended] The use of claim 293, wherein the composition is administered parenterally.
[295" claim-type="Currently amended] The use of claim 293, wherein the composition is administered mucosally.
[296" claim-type="Currently amended] The use of claim 293, wherein the composition is administered by subcutaneous or intramuscular injection.
[297" claim-type="Currently amended] (a) one or more proteins encoded by an open reading frame of Neisseria species (ORF2086) encoding a cross-reactive immunogenic antigen that provides immunogenicity against infection by Neisseria meningitidis serogroup B in a subject; or
(b) at least one immunogenic portion of at least one protein described in (a); or
(c) at least one biological equivalent of at least one protein described in (a) or an immunogenic fragment described in (b)
A method of making a composition comprising expressing in a host cell a nucleic acid sequence encoding any of the above.
[298" claim-type="Currently amended] 297. The method of claim 297, wherein the nucleic acid sequence is expressed in vivo.
[299" claim-type="Currently amended] 297. The method of claim 297, wherein the nucleic acid sequence is expressed in vitro.
[300" claim-type="Currently amended] 297. The method of claim 297, further comprising binding the P4 leader sequence (SEQ ID NO: 322).
[301" claim-type="Currently amended] 297. The method of claim 297, wherein the one or more proteins comprise any one of SEQ ID NOs: 254 to 299.
[302" claim-type="Currently amended] (a) one or more proteins encoded by an open reading frame of Neisseria species (ORF2086) encoding a cross-reactive immunogenic antigen that provides immunogenicity against infection by Neisseria meningitidis serogroup B in a subject, or Encoding one or more immunogenic portions or biological equivalents of said one or more proteins; or
(b) hybridize to any of the polynucleotides described in (a) under stringent conditions
Process for preparing a composition comprising isolating and purifying one or more polynucleotides from Neisseria meningitidis
[303" claim-type="Currently amended] 302. The method of claim 302, wherein the stringent conditions are highly stringent Southern hybridization conditions.
[304" claim-type="Currently amended] A method of making a composition comprising isolation and purification of any of the proteins, immunogenic portions, or biological equivalents described herein from Neisseria species.
[305" claim-type="Currently amended] A method of making an antibody composition comprising recovering the antibody from the animal after introducing the composition comprising any of the proteins, immunogenic portions or biological equivalents described herein into the animal.
[306" claim-type="Currently amended] A method of inducing an immune response in a mammal comprising administering to the mammal an effective amount of one or more compositions of any one of claims 1-289.
[307" claim-type="Currently amended] 306. The method of claim 306, wherein the composition is administered parenterally.
[308" claim-type="Currently amended] 306. The method of claim 306, wherein the composition is administered mucosally.
[309" claim-type="Currently amended] A method of preventing or treating bacterial meningitis in a mammal, comprising administering to the mammal an effective amount of one or more compositions of any one of claims 1-289.
[310" claim-type="Currently amended] 309. The method of claim 309, wherein the composition is parenterally administered.
[311" claim-type="Currently amended] 309. The method of claim 309, wherein the composition is administered mucosally.
[312" claim-type="Currently amended] 309. The method of claim 309, wherein the composition is administered by subcutaneous or intramuscular injection.
[313" claim-type="Currently amended] Mammalian antibody compositions comprising an effective amount of an antibody that immunospecifically binds an even numbered sequence of any one of SEQ ID NOS: 2-252 or a protein, an immunogenic portion, or a biological equivalent comprising the amino acid sequence of any of SEQ ID NOs: 254-299 A method for preventing or treating bacterial meningitis in a mammal, comprising administering to the same.
[Claim 313] 313. The method of claim 312, wherein the antibody composition is administered parenterally.
[314" claim-type="Currently amended] 313. The method of claim 312, wherein the antibody composition is administered mucosally.
[315" claim-type="Currently amended] 338. The method of claim 312, wherein the antibody composition is administered by subcutaneous or intramuscular injection.
[316" claim-type="Currently amended] (a) one or more proteins comprising the amino acid sequence of any of SEQ ID NOs: 2 to 252 or any of SEQ ID NOs: 254 to 299;
(b) one or more proteins encoded by a polynucleotide that hybridizes to a polynucleotide comprising the nucleic acid sequence of any of SEQ ID NOS: 1-253 under stringent conditions;
(c) at least one immunogenic portion of at least one protein described in (a) or (b); or
(d) at least one biological equivalent of at least one protein described in (a) or (b) or an immunogenic fragment described in (c)
A method of making a composition comprising expressing in a host cell a nucleic acid sequence encoding any of the above.
[317" claim-type="Currently amended] 316. The method of claim 316, wherein the nucleic acid sequence is expressed in vivo.
[318" claim-type="Currently amended] 316. The method of claim 316, wherein the nucleic acid sequence is expressed in vitro.
[319" claim-type="Currently amended] 316. The method of claim 316, wherein the vector is a plasmid.
[320" claim-type="Currently amended] 316. The method of claim 316, wherein the vector is a phage.
[321" claim-type="Currently amended] 316. The method of claim 316, further comprising coupling a non-natural leader sequence with the one or more isolated polynucleotides.
[322" claim-type="Currently amended] 316. The method of claim 316, wherein the non-natural leader sequence is a P4 leader sequence (SEQ ID NO: 267).
[323" claim-type="Currently amended] x is any amino acid;
The region of amino acid position 5 to amino acid position 9 is any 0 to 5 amino acids;
The region of amino acid position 67 to amino acid position 69 is any 0 to 3 amino acids;
Amino acid position 156 is any 0 to 1 amino acid
A method of making a composition comprising isolating and purifying one or more isolated proteins comprising an amino acid sequence of SEQ ID NO: 300 from a Neisseria species.
[324" claim-type="Currently amended] 323. The method of claim 323, further comprising introducing a non-natural leader sequence into one or more isolated polynucleotides.
[325" claim-type="Currently amended] 323. The composition of claim 323, wherein the non-natural leader sequence is a P4 leader sequence (SEQ ID NO: 322).
[326" claim-type="Currently amended] (a) one or more proteins comprising an even numbered amino acid sequence of any of SEQ ID NOs: 2 to 252 or any one of SEQ ID NOs: 254 to 259, 260 to 278, or 279 to 299; or
(b) one or more proteins encoded by a polynucleotide that hybridizes to a polynucleotide comprising the nucleic acid sequence of any of the odd-numbered sequences 1-253 under stringent conditions
A process for producing a composition comprising any of the isolated from Neisseria species.
[327" claim-type="Currently amended] 326. The method of claim 326, wherein the stringent conditions are highly stringent southern hybridization conditions.
[328" claim-type="Currently amended] (a) one or more proteins comprising an even numbered amino acid sequence of any of SEQ ID NOs: 2 to 252 or any one of SEQ ID NOs: 254 to 259, 260 to 278, or 279 to 299; or
(b) one or more proteins encoded by polynucleotides that hybridize to the polynucleotides of any of the odd-numbered sequences 1-253 under stringent conditions
A method for producing an antibody composition comprising recovering an antibody from an animal after introducing the composition comprising the animal into an animal.
[329" claim-type="Currently amended] 328. The method of claim 328, wherein the stringent conditions are highly stringent southern hybridization conditions.
[330" claim-type="Currently amended] (a) encodes one or more isolated proteins comprising the amino acid sequence of any one of SEQ ID NOs: 254-259, 260-278 or 279-299, or
(b) hybridize to any of the polynucleotides described in (a) under stringent conditions
Transformed / transfected or infected cell lines comprising recombinant cells expressing nucleic acid sequences.
[331" claim-type="Currently amended] (a) one or more proteins encoded by an open reading frame of Neisseria species (ORF2086) encoding a cross-reactive immunogenic antigen that provides immunogenicity against infection by Neisseria meningitidis serogroup B in a subject, or Encoding one or more immunogenic portions or biological equivalents of said one or more proteins or (b) hybridizing to any of the polynucleotides of (a) under stringent conditions
Recombinant cells expressing nucleic acid sequences; or
(c) one or more polypeptides encoded by any of (a) or (b); Or (d) a recombinant cell expressing a nucleic acid sequence encoding one or more polypeptides comprising an even numbered amino acid of any one of SEQ ID NOs: 2 to 252.
Transformed / transfected or infected cell line comprising a.
[332" claim-type="Currently amended] 331. The transformed / transfected or infected cell line of claim 331, wherein the polypeptide is a monoclonal antibody.
[333" claim-type="Currently amended] 331. The transformed / transfected or infected cell line of claim 331, wherein the recombinant cell is a hybridoma.
[334" claim-type="Currently amended] 331. The transformed / transfected or infected cell line of claim 331, wherein the recombinant cell is trioma.
[335" claim-type="Currently amended] (a) one or more polynucleotides encoding a protein comprising any of the even numbered sequences 2 to 252;
(b) one or more polynucleotides comprising the nucleic acid sequence of any of the odd numbered sequences 1-253;
(c) one or more polynucleotides that hybridize to any of (a) or (b) under stringent conditions
A recombinant cell expressing a nucleic acid sequence comprising a; or
(d) one or more polypeptides encoded by any of (a), (b) or (c); or
(e) one or more polypeptides comprising the amino acids of any of the even numbers SEQ ID NOs: 2-252
A recombinant cell expressing a nucleic acid sequence encoding
Transformed / transfected or infected cell line comprising a.
[336" claim-type="Currently amended] 335. The transformed / transfected or infected cell line of claim 335, wherein the polypeptide is a monoclonal antibody.
[337" claim-type="Currently amended] 335. The transformed / transfected or infected cell line of claim 335, wherein the recombinant cell is a hybridoma.
[338" claim-type="Currently amended] 335. The transformed / transfected or infected cell line of claim 335, wherein the recombinant cell is a trioma.
[339" claim-type="Currently amended] A method of identifying an immunogenic protein comprising detecting bactericidal activity in a sample tested for ORF2086 antiserum.
[340" claim-type="Currently amended] A method of identifying an immunogenic protein comprising detecting a polynucleotide in a sample tested against an ORF2086 nucleic acid probe.
[341" claim-type="Currently amended] A composition substantially the same as any one of claims 1-289.
[342" claim-type="Currently amended] Uses substantially the same as described in any of claims 290 to 296.

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引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

法律状态:
2001-10-11|Priority to US32810101P

---

2001-10-11|Priority to US60/328,101

---

2002-08-30|Priority to US40693402P

---

2002-08-30|Priority to US60/406,934

---

2002-10-11|Application filed by 와이어쓰 홀딩스 코포레이션

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2002-10-11|Priority to PCT/US2002/032369

---

2004-07-27|Publication of KR20040066793A

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2011-09-28|Application granted

---

2011-09-28|Publication of KR101068318B1

---

2013-11-01|First worldwide family litigation filed

优先权:

---

申请号 | 申请日 | 专利标题

---

US32810101P| true| 2001-10-11|2001-10-11|

---

US60/328,101|2001-10-11|

---

US40693402P| true| 2002-08-30|2002-08-30|

---

US60/406,934|2002-08-30|

---

PCT/US2002/032369|WO2003063766A2|2001-10-11|2002-10-11|Novel immunogenic compositions for the prevention and treatment of meningococcal disease|