Advances in structure-based vaccine design

Current Opinion in Virology

Volumn 3, Issue 3, 2013, Pages 322-331

  Kulp, Daniel W ^a   Schief, William R ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 CYCLOHEXYLAMINO 1 (1 NAPHTHYLOXY) 2 BUTANOL; ANTIGEN; ENVELOPE PROTEIN; EPITOPE; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; LIPID LINKED PROTEIN; NEUTRALIZING ANTIBODY; RNA VACCINE; SCAFFOLD PROTEIN;

ANTIGEN BINDING; ANTIGEN STRUCTURE; ARTICLE; B LYMPHOCYTE; CRYSTAL STRUCTURE; DRUG DESIGN; DRUG RESEARCH; DRUG SCREENING; HEPATITIS C VIRUS; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IMMUNIZATION; IN VITRO STUDY; INFLUENZA VIRUS; MENINGITIS; MUTAGENESIS; NEISSERIA; NONHUMAN; PRIORITY JOURNAL; SOMATIC MUTATION; VACCINATION;

EID: 84880295369     PISSN: 18796257     EISSN: 18796265     Source Type: Journal    
DOI: 10.1016/j.coviro.2013.05.010     Document Type: Review

References (89)

1. S. Ozawa, A. Mirelman, M.L. Stack, D.G. Walker, and O.S. Levine Cost-effectiveness and economic benefits of vaccines in low- and middle-income countries: a systematic review Vaccine 31 2012 96 108
2. R. Lozano, M. Naghavi, K. Foreman, S. Lim, K. Shibuya, V. Aboyans, J. Abraham, T. Adair, R. Aggarwal, and S.Y. Ahn Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010 Lancet 380 2012 2095 2128
3. S.A. Plotkin Correlates of protection induced by vaccination Clin Vaccine Immunol 17 2010 1055 1065
4. S.A. Plotkin, and S.A. Plotkin Correlates of vaccine-induced immunity Clin Infect Dis 47 2008 401 409
5. I.J. Amanna, I. Messaoudi, and M.K. Slifka Protective immunity following vaccination: how is it defined? Hum Vaccines 4 2008 316 319
6. I.J. Amanna, and M.K. Slifka Wanted, dead or alive: new viral vaccines Antiviral Res 84 2009 119 130
7. FDA: List of Vaccine Approvals. URL: http://www.fda.gov/ BiologicsBloodVaccines/Vaccines/ApprovedProducts/
8. S.A. Plotkin, W.A. Orenstein, and P.A. Offit Vaccines 2008 Elsevier Philadelphia
9. B. Petsch, M. Schnee, A.B. Vogel, E. Lange, B. Hoffmann, D. Voss, T. Schlake, A. Thess, K.-J. Kallen, and L. Stitz Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection Nat Biotechnol 30 2012 1210 1216
10. A.J. Geall, A. Verma, G.R. Otten, C.A. Shaw, A. Hekele, K. Banerjee, Y. Cu, C.W. Beard, L.A. Brito, and T. Krucker Nonviral delivery of self-amplifying RNA vaccines PNAS 109 2012 14604 14609
11. S. Rerks-Ngarm, P. Pitisuttithum, S. Nitayaphan, J. Kaewkungwal, J. Chiu, R. Paris, N. Premsri, C. Namwat, M. de Souza, and E. Adams Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand N Engl J Med 361 2009 2209 2220
12. C.-J. Wei, J.C. Boyington, P.M. McTamney, W.-P. Kong, M.B. Pearce, L. Xu, H. Andersen, S. Rao, T.M. Tumpey, and Z.-Y. Yang Induction of broadly neutralizing H1N1 influenza antibodies by vaccination Science 329 2010 1060 1064
13. S.J. Draper, and J.L. Heeney Viruses as vaccine vectors for infectious diseases and cancer Nat Rev Microbiol 8 2010 62 73
14. J.E. Ledgerwood, C.-J. Wei, Z. Hu, I.J. Gordon, M.E. Enama, C.S. Hendel, P.M. McTamney, M.B. Pearce, H.M. Yassine, and J.C. Boyington DNA priming and influenza vaccine immunogenicity: two phase 1 open label randomised clinical trials Lancet Infect Dis 11 2011 916 924
15. J.E. Ledgerwood, and B.S. Graham DNA vaccines: a safe and efficient platform technology for responding to emerging infectious diseases Hum Vaccines 5 2009 623 626
16. S. Lu Heterologous prime-boost vaccination Curr Opin Immunol 21 2009 346 351
17. D. Carter, and S.G. Reed Role of adjuvants in modeling the immune response Curr Opin HIV AIDS 5 2010 409 413
18. R.L. Coffman, A. Sher, and R.A. Seder Vaccine adjuvants: putting innate immunity to work Immunity 33 2010 492 503
19. F. Wegmann, K.H. Gartlan, A.M. Harandi, S.A. Brinckmann, M. Coccia, W.R. Hillson, W.L. Kok, S. Cole, L.-P. Ho, and T. Lambe Polyethyleneimine is a potent mucosal adjuvant for viral glycoprotein antigens Nat Biotechnol 30 2012 883 888
20. S.R. Wiley, V.S. Raman, A. Desbien, H.R. Bailor, R. Bhardwaj, A.R. Shakri, S.G. Reed, C.E. Chitnis, and D. Carter Targeting TLRs expands the antibody repertoire in response to a malaria vaccine Sci Transl Med 3 2011 93ra69
21. M.A. Arias, G.A. Van Roey, J.S. Tregoning, M. Moutaftsi, R.N. Coler, H.P. Windish, S.G. Reed, D. Carter, and R.J. Shattock Glucopyranosyl lipid adjuvant (GLA), a synthetic TLR4 agonist, promotes potent systemic and mucosal responses to intranasal immunization with HIVgp140 PLoS ONE 7 2012 e41144
22. R.P.J. Lai, M.S. Seaman, P. Tonks, F. Wegmann, D.J. Seilly, S.D.W. Frost, C.C. LaBranche, D.C. Montefiori, A.K. Dey, and I.K. Srivastava Mixed adjuvant formulations reveal a new combination that elicit antibody response comparable to Freund's adjuvants PLoS ONE 7 2012 e35083
23. J.J. Moon, H. Suh, A. Bershteyn, M.T. Stephan, H. Liu, B. Huang, M. Sohail, S. Luo, S. Ho Um, and H. Khant Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses Nat Mater 10 2011 243 251
24. S.P. Kasturi, I. Skountzou, R.A. Albrecht, D. Koutsonanos, T. Hua, H.I. Nakaya, R. Ravindran, S. Stewart, M. Alam, and M. Kwissa Programming the magnitude and persistence of antibody responses with innate immunity Nature 470 2011 543 547
25. J.J. Moon, H. Suh, A.V. Li, C.F. Ockenhouse, A. Yadava, and D.J. Irvine Enhancing humoral responses to a malaria antigen with nanoparticle vaccines that expand Tfh cells and promote germinal center induction PNAS 109 2012 1080 1085
26. T.D. Querec, R.S. Akondy, E.K. Lee, W. Cao, H.I. Nakaya, D. Teuwen, A. Pirani, K. Gernert, J. Deng, and B. Marzolf Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans Nat Immunol 10 2009 116 125
27. H.I. Nakaya, J. Wrammert, E.K. Lee, L. Racioppi, S. Marie-Kunze, W.N. Haining, A.R. Means, S.P. Kasturi, N. Khan, and G.-M. Li Systems biology of vaccination for seasonal influenza in humans Nat Immunol 12 2011 786 795
28. H.I. Nakaya, S. Li, and B. Pulendran Systems vaccinology: learning to compute the behavior of vaccine induced immunity Wiley Interdiscip Rev Syst Biol Med 4 2012 193 205
29. R. Rappuoli Bridging the knowledge gaps in vaccine design Nat Biotechnol 25 2007 1361 1366
30. C. Donati, and R. Rappuoli Reverse vaccinology in the 21st century: improvements over the original design Ann N Y Acad Sci 2013 10.1111/nyas.12046
31. P.R. Dormitzer, J.B. Ulmer, and R. Rappuoli Structure-based antigen design: a strategy for next generation vaccines Trends Biotechnol 26 2008 659 667
32. W.R. Schief, Y.-E.A. Ban, and L. Stamatatos Challenges for structure-based HIV vaccine design Curr Opin HIV AIDS 4 2009 431 440
33. D.R. Burton, P. Poignard, R.L. Stanfield, and I.A. Wilson Broadly neutralizing antibodies present new prospects to counter highly antigenically diverse viruses Science 337 2012 183 186
34. J.-P. Julien, P.S. Lee, and I.A. Wilson Structural insights into key sites of vulnerability on HIV-1 Env and influenza HA Immunol Rev 250 2012 180 198
35. P.R. Dormitzer, G. Grandi, and R. Rappuoli Structural vaccinology starts to deliver Nat Rev Microbiol 10 2012 807 813
36. D.R. Burton Antibodies, viruses and vaccines Nat Rev Immunol 2 2002 706 713
37. X. Wu, Z.-Y. Yang, Y. Li, C.-M. Hogerkorp, W.R. Schief, M.S. Seaman, T. Zhou, S.D. Schmidt, L. Wu, and L. Xu Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1 Science 329 2010 856 861
38. T. Zhou, I. Georgiev, X. Wu, Z.-Y. Yang, K. Dai, A. Finzi, Y.D. Kwon, J.F. Scheid, W. Shi, and L. Xu Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01 Science 329 2010 811 817
39. X. Wu, T. Zhou, J. Zhu, B. Zhang, I. Georgiev, C. Wang, X. Chen, N.S. Longo, M. Louder, and K. McKee Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing Science 333 2011 1593 1602
40. J.F. Scheid, H. Mouquet, B. Ueberheide, R. Diskin, F. Klein, T.Y.K. Oliveira, J. Pietzsch, D. Fenyo, A. Abadir, and K. Velinzon Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding Science 333 2011 1633 1637
41. A.P. West, R. Diskin, M.C. Nussenzweig, and P.J. Bjorkman Structural basis for germ-line gene usage of a potent class of antibodies targeting the CD4-binding site of HIV-1 gp120 PNAS 109 2012 E2083 E2090
42. I. Mikell, D.N. Sather, S.A. Kalams, M. Altfeld, G. Alter, and L. Stamatatos Characteristics of the earliest cross-neutralizing antibody response to HIV-1 PLoS Pathog 7 2011 e1001251
43. A.T. McGuire, S. Hoot, A.M. Dreyer, A. Lippy, A. Stuart, K.W. Cohen, J. Jardine, S. Menis, J.F. Scheid, and A.P. West Engineering HIV envelope protein to activate germline B cell receptors of broadly neutralizing anti-CD4 binding site antibodies J Exp Med 2013 10.1084/jem.20122824
44. J. Jardine, J.-P. Julien, S. Menis, T. Ota, O. Kalyuzhniy, A. McGuire, D. Sok, P.-S. Huang, S. MacPherson, and M. Jones Rational HIV immunogen design to target specific germline B cell receptors Science 2013 10.1126/science.1234150
45. A. Leaver-Fay, M. Tyka, S.M. Lewis, O.F. Lange, J. Thompson, R. Jacak, K. Kaufman, P.D. Renfrew, C.A. Smith, and W. Sheffler ROSETTA3: an object-oriented software suite for the simulation and design of macromolecules Methods Enzymol. 487 2011 545 574
46. M.L. Azoitei, B.E. Correia, Y.-E.A. Ban, C. Carrico, O. Kalyuzhniy, L. Chen, A. Schroeter, P.-S. Huang, J.S. McLellan, and P.D. Kwong Computation-guided backbone grafting of a discontinuous motif onto a protein scaffold Science 334 2011 373 376
47. H.-X. Liao, R. Lynch, T. Zhou, F. Gao, S.M. Alam, S.D. Boyd, A.Z. Fire, K.M. Roskin, C.A. Schramm, and Z. Zhang Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus Nature 2013 10.1038/nature12053
48. Y. Okuno, Y. Isegawa, F. Sasao, and S. Ueda A common neutralizing epitope conserved between the hemagglutinins of influenza A virus H1 and H2 strains J Virol 67 1993 2552 2558
49. J. Sui, W.C. Hwang, S. Perez, G. Wei, D. Aird, L. Chen, E. Santelli, B. Stec, G. Cadwell, and M. Ali Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses Nat Struct Mol Biol 16 2009 265 273
50. D.C. Ekiert, G. Bhabha, M.-A. Elsliger, R.H.E. Friesen, M. Jongeneelen, M. Throsby, J. Goudsmit, and I.A. Wilson Antibody recognition of a highly conserved influenza virus epitope Science 324 2009 246 251
51. D. Corti, A.L. Suguitan, D. Pinna, C. Silacci, B.M. Fernandez-Rodriguez, F. Vanzetta, C. Santos, C.J. Luke, F.J. Torres-Velez, and N.J. Temperton Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine J Clin Invest 120 2010 1663 1673
52. S. Sakabe, K. Iwatsuki-Horimoto, T. Horimoto, C.A. Nidom, Mt. Quynh Le, R. Takano, R. Kubota-Koketsu, Y. Okuno, M. Ozawa, and Y. Kawaoka A cross-reactive neutralizing monoclonal antibody protects mice from H5N1 and pandemic (H1N1) 2009 virus infection Antiviral Res 88 2010 249 255
53. J. Wrammert, D. Koutsonanos, G.-M. Li, S. Edupuganti, J. Sui, M. Morrissey, M. McCausland, I. Skountzou, M. Hornig, and W.I. Lipkin Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection J Exp Med 208 2011 181 193
54. D.C. Ekiert, R.H.E. Friesen, G. Bhabha, T. Kwaks, M. Jongeneelen, W. Yu, C. Ophorst, F. Cox, H.J.W.M. Korse, and B. Brandenburg A highly conserved neutralizing epitope on group 2 influenza A viruses Science 333 2011 843 850
55. D. Corti, J. Voss, S.J. Gamblin, G. Codoni, A. Macagno, D. Jarrossay, S.G. Vachieri, D. Pinna, A. Minola, and F. Vanzetta A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins Science 333 2011 850 856
56. C. Dreyfus, N.S. Laursen, T. Kwaks, D. Zuijdgeest, R. Khayat, D.C. Ekiert, J.H. Lee, Z. Metlagel, M.V. Bujny, and M. Jongeneelen Highly conserved protective epitopes on influenza B viruses Science 337 2012 1343 1348
57. D. Lingwood, P.M. McTamney, H.M. Yassine, J.R.R. Whittle, X. Guo, J.C. Boyington, C.-J. Wei, and G.J. Nabel Structural and genetic basis for development of broadly neutralizing influenza antibodies Nature 489 2012 566 570
58. S. Koide, X. Yang, X. Huang, J.J. Dunn, and B.J. Luft Structure-based design of a second-generation lyme disease vaccine based on a C-terminal fragment of Borrelia burgdorferi OspA J Mol Biol 350 2005 290 299
59. G. Bommakanti, M.P. Citron, R.W. Hepler, C. Callahan, G.J. Heidecker, T.A. Najar, X. Lu, J.G. Joyce, J.W. Shiver, and D.R. Casimiro Design of an HA2-based Escherichia coli expressed influenza immunogen that protects mice from pathogenic challenge PNAS 107 2010 13701 13706
60. G. Bommakanti, X. Lu, M.P. Citron, T.A. Najar, G.J. Heidecker, J.ter Meulen, R. Varadarajan, and X. Liang Design of Escherichia coli-expressed stalk domain immunogens of H1N1 hemagglutinin that protect mice from lethal challenge J Virol 86 2012 13434 13444
61. J. Steel, A.C. Lowen, T.T. Wang, M. Yondola, Q. Gao, K. Haye, A. García-Sastre, and P. Palese Influenza virus vaccine based on the conserved hemagglutinin stalk domain MBio 1 2010 doi:pii: e00018-10.10.1128/ mBio.00018-10
62. M.G. Joyce, M. Kanekiyo, L. Xu, C. Biertümpfel, J.C. Boyington, S. Moquin, W. Shi, X. Wu, Y. Yang, and Z.-Y. Yang Outer domain of HIV-1 gp120: antigenic optimization, structural malleability, and crystal structure with antibody VRC-PG04 J Virol 87 2013 2294 2306
63. S. Bhattacharyya, R.E. Rajan, Y. Swarupa, U. Rathore, A. Verma, R. Udaykumar, and R. Varadarajan Design of a non-glycosylated outer domain-derived HIV-1 gp120 immunogen that binds to CD4 and induces neutralizing antibodies J Biol Chem 285 2010 27100 27110
64. R. Pejchal, K.J. Doores, L.M. Walker, R. Khayat, P.-S. Huang, S.-K. Wang, R.L. Stanfield, J.-P. Julien, A. Ramos, and M. Crispin A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield Science 334 2011 1097 1103
65. X. Yang, V. Tomov, S. Kurteva, L. Wang, X. Ren, M.K. Gorny, S. Zolla-Pazner, and J. Sodroski Characterization of the outer domain of the gp120 glycoprotein from human immunodeficiency virus type 1 J Virol 78 2004 12975 12986
66. S. Bhattacharyya, P. Singh, U. Rathore, M. Purwar, D. Wagner, H. Arendt, J. Destefano, C.C. Labranche, D.C. Montefiori, and S. Phogat Design of an E. coli expressed HIV-1 gp120 fragment immunogen that binds to b12 and induces broad and potent neutralizing antibodies J Biol Chem 2013 10.1074/jbc.M112. 425959
67. J.R. Compton, P.M. Legler, B.V. Clingan, M.A. Olson, and C.B. Millard Introduction of a disulfide bond leads to stabilization and crystallization of a ricin immunogen Protein Struct Funct Bioinform 79 2011 1048 1060
68. M. Soriani, P. Petit, R. Grifantini, R. Petracca, G. Gancitano, E. Frigimelica, F. Nardelli, C. Garcia, S. Spinelli, and G. Scarabelli Exploiting antigenic diversity for vaccine design: the chlamydia ArtJ paradigm J Biol Chem 285 2010 30126 30138
69. A. Nuccitelli, R. Cozzi, L.J. Gourlay, D. Donnarumma, F. Necchi, N. Norais, J.L. Telford, R. Rappuoli, M. Bolognesi, and D. Maione Structure-based approach to rationally design a chimeric protein for an effective vaccine against Group B Streptococcus infections PNAS 108 2011 10278 10283
70. G. Ofek, F.J. Guenaga, W.R. Schief, J. Skinner, D. Baker, R. Wyatt, and P.D. Kwong Elicitation of structure-specific antibodies by epitope scaffolds PNAS 107 2010 17880 17887
71. B.E. Correia, Y.-E.A. Ban, M.A. Holmes, H. Xu, K. Ellingson, Z. Kraft, C. Carrico, E. Boni, D.N. Sather, and C. Zenobia Computational design of epitope-scaffolds allows induction of antibodies specific for a poorly immunogenic HIV vaccine epitope Structure 18 2010 1116 1126
72. M.L. Azoitei, Y.-E.A. Ban, J.-P. Julien, S. Bryson, A. Schroeter, O. Kalyuzhniy, J.R. Porter, Y. Adachi, D. Baker, and E.F. Pai Computational design of high-affinity epitope scaffolds by backbone grafting of a linear epitope J Mol Biol 415 2012 175 192
73. G. Ofek, M. Tang, A. Sambor, H. Katinger, J.R. Mascola, R. Wyatt, and P.D. Kwong Structure and mechanistic analysis of the anti-human immunodeficiency virus type 1 antibody 2F5 in complex with its gp41 epitope J Virol 78 2004 10724 10737
74. Z.-Y.J. Sun, K.J. Oh, M. Kim, J. Yu, V. Brusic, L. Song, Z. Qiao, J. Wang, G. Wagner, and E.L. Reinherz HIV-1 broadly neutralizing antibody extracts its epitope from a kinked gp41 ectodomain region on the viral membrane Immunity 28 2008 52 63
75. H. Xu, L. Song, M. Kim, M.A. Holmes, Z. Kraft, G. Sellhorn, E.L. Reinherz, L. Stamatatos, and R.K. Strong Interactions between lipids and human anti-HIV antibody 4E10 can be reduced without ablating neutralizing activity J Virol 84 2010 1076 1088
76. E.M. Scherer, D.P. Leaman, M.B. Zwick, A.J. McMichael, and D.R. Burton Aromatic residues at the edge of the antibody combining site facilitate viral glycoprotein recognition through membrane interactions PNAS 107 2010 1529 1534
77. G. Ofek, K. McKee, Y. Yang, Z.-Y. Yang, J. Skinner, F.J. Guenaga, R. Wyatt, M.B. Zwick, G.J. Nabel, and J.R. Mascola Relationship between antibody 2F5 neutralization of HIV-1 and hydrophobicity of its heavy chain third complementarity-determining region J Virol 84 2010 2955 2962
78. M. Kim, Sun Z-YJ, K.D. Rand, X. Shi, L. Song, Y. Cheng, A.F. Fahmy, S. Majumdar, G. Ofek, and Y. Yang Antibody mechanics on a membrane-bound HIV segment essential for GP41-targeted viral neutralization Nat Struct Mol Biol 18 2011 1235 1243
79. G. Yang, T.M. Holl, Y. Liu, Y. Li, X. Lu, N.I. Nicely, T.B. Kepler, S.M. Alam, H.-X. Liao, and D.W. Cain Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies J Exp Med 210 2013 241 256
80. J. Huang, G. Ofek, L. Laub, M.K. Louder, N.A. Doria-Rose, N.S. Longo, H. Imamichi, R.T. Bailer, B. Chakrabarti, and S.K. Sharma Broad and potent neutralization of HIV-1 by a gp41-specific human antibody Nature 491 2012 406 412
81. J.S. Klein, P.N.P. Gnanapragasam, R.P. Galimidi, C.P. Foglesong, A.P. West, and P.J. Bjorkman Examination of the contributions of size and avidity to the neutralization mechanisms of the anti-HIV antibodies b12 and 4E10 PNAS 106 2009 7385 7390
82. P. Roben, J.P. Moore, M. Thali, J. Sodroski, C.F. Barbas, and D.R. Burton Recognition properties of a panel of human recombinant Fab fragments to the CD4 binding site of gp120 that show differing abilities to neutralize human immunodeficiency virus type 1 J Virol 68 1994 4821 4828
83. T. Zhou, L. Xu, B. Dey, A.J. Hessell, D.V. Ryk, S.-H. Xiang, X. Yang, M.-Y. Zhang, M.B. Zwick, and J. Arthos Structural definition of a conserved neutralization epitope on HIV-1 gp120 Nature 445 2007 732 737
84. J.K. Scott, R. Pantophlet, and L. Craig Complex binding sites made to order Nat Biotechnol 30 2012 154 155
85. M. Pizza, V. Scarlato, V. Masignani, M.M. Giuliani, B. Aricò, M. Comanducci, G.T. Jennings, L. Baldi, and E. Bartolini Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing Science 287 2000 1816 1820
86. V. Masignani, M. Comanducci, M.M. Giuliani, S. Bambini, J. Adu-Bobie, B. Aricò, B. Brunelli, A. Pieri, L. Santini, and S. Savino Vaccination against Neisseria meningitidis using three variants of the lipoprotein GNA1870 J Exp Med 197 2003 789 799
87. D.M. Granoff Review of meningococcal group B vaccines Clin Infect Dis 50 2010 S54 S65
88. M. Scarselli, B. Aricò, B. Brunelli, S. Savino, F.D. Marcello, E. Palumbo, D. Veggi, L. Ciucchi, E. Cartocci, and M.J. Bottomley Rational design of a meningococcal antigen inducing broad protective immunity Sci Transl Med 3 2011 91ra62
89. N.D. Rubinstein, I. Mayrose, D. Halperin, D. Yekutieli, J.M. Gershoni, and T. Pupko Computational characterization of B-cell epitopes Mol Immunol 45 2008 3477 3489