Prospects for antibody-based universal influenza vaccines in the context of widespread pre-existing immunity

Expert Review of Vaccines

Volumn 14, Issue 9, 2015, Pages 1227-1239

  Wheatley, Adam Kenneth ^a   Kent, Stephen John ^a,b  

^a UNIVERSITY OF MELBOURNE   (Australia)

^b MONASH UNIVERSITY   (Australia)

Author keywords

antigenic sin; influenza; pandemic; universal; vaccine

Indexed keywords

ANTIBODY; DNA VACCINE; EPITOPE; INFLUENZA VACCINE; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY C179; NEUTRALIZING ANTIBODY; UNCLASSIFIED DRUG; VIRUS HEMAGGLUTININ; VIRUS PROTEIN; INFLUENZA VIRUS HEMAGGLUTININ; VIRUS ANTIBODY;

ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; ANTIBODY RESPONSE; CLINICAL ASSESSMENT; CROSS PROTECTION; DRUG EFFICACY; DRUG FORMULATION; HEMAGGLUTINATION INHIBITION; HUMAN; HUMORAL IMMUNITY; IMMUNOGENICITY; IN VITRO STUDY; IN VIVO STUDY; INFLUENZA A; INFLUENZA VACCINATION; INFLUENZA VIRUS A H10N8; INFLUENZA VIRUS A H3N2; INFLUENZA VIRUS A H5N1; INFLUENZA VIRUS A H7N9; NONHUMAN; PANDEMIC INFLUENZA; PRIORITY JOURNAL; PROSPECTIVE STUDY; REVIEW; SEASONAL INFLUENZA; VIRUS IMMUNITY; VIRUS STRAIN; ANIMAL; BLOOD; CROSS REACTION; DRUG DEVELOPMENT; IMMUNOLOGY; INFLUENZA, HUMAN; ISOLATION AND PURIFICATION; ORTHOMYXOVIRIDAE INFECTIONS; TRENDS; VETERINARY;

ANIMALS; ANTIBODIES, VIRAL; CROSS PROTECTION; CROSS REACTIONS; DRUG DISCOVERY; HEMAGGLUTININ GLYCOPROTEINS, INFLUENZA VIRUS; HUMANS; INFLUENZA VACCINES; INFLUENZA, HUMAN; ORTHOMYXOVIRIDAE INFECTIONS;

EID: 84939431393     PISSN: 14760584     EISSN: 17448395     Source Type: Journal    
DOI: 10.1586/14760584.2015.1068125     Document Type: Review

References (149)

1. Tong S, Zhu X, Li Y, et al. New world bats harbor diverse influenza A viruses. PLoS Pathog 2013;9:e1003657
2. Taubenberger JK, Kash JC. Influenza virus evolution, host adaptation, and pandemic formation. Cell Host Microbe 2010;7: 440-51
3. Bodewes R, Morick D, de Mutsert G, et al. Recurring influenza B virus infections in seals. Emerg Infect Dis 2013;19:511-12
4. Novel Swine-Origin Influenza A, Dawood FS, Jain S, et al. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009;360: 2605-15
5. Garten RJ, Davis CT, Russell CA, et al. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science 2009;325:197-201
6. Kelly H, Peck HA, Laurie KL, et al. The age-specific cumulative incidence of infection with pandemic influenza H1N1. 2009 was similar in various countries prior to vaccination. PloS one 2011;6:e21828
7. Dawood FS, Iuliano AD, Reed C, et al. Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study. Lancet Infect Dis 2012;12:687-95
8. Simonsen L, Spreeuwenberg P, Lustig R, et al. Global mortality estimates for the 2009 Influenza Pandemic from the GLaMOR project: a modeling study. PLoS medicine 2013;10:e1001558
9. Jhung MA, Epperson S, Biggerstaff M, et al. Outbreak of variant influenza A (H3N2) virus in the United States. Clin Infect Dis 2013;57:1703-12
10. To KK, Tsang AK, Chan JF, et al. Emergence in China of human disease due to avian influenza A(H10N8)-cause for concern? J Infect 2014;68:205-15
11. Lam TT, Wang J, Shen Y, et al. The genesis and source of the H7N9 influenza viruses causing human infections in China. Nature 2013;502:241-4
12. Guan Y, Smith GJ. The emergence and diversification of panzootic H5N1 influenza viruses. Virus Res 2013;178:35-43
13. Epstein SL, Price GE. Cross-protective immunity to influenza A viruses. Expert Rev Vaccines 2010;9:1325-41
14. Quinones-Parra S, Loh L, Brown LE, et al. Universal immunity to influenza must outwit immune evasion. Front Microbiol 2014;5:285
15. Valkenburg SA, Rutigliano JA, Ellebedy AH, et al. Immunity to seasonal and pandemic influenza A viruses. Microbes Infect 2011;13: 489-501
16. Whittle JR, Zhang R, Khurana S, et al. Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin. Proc Nat Acad Sci USA 2011;108:14216-21
17. Ekiert DC, Kashyap AK, Steel J, et al. Cross-neutralization of influenza A viruses mediated by a single antibody loop. Nature 2012;489:526-32
18. Corti D, Suguitan AL, Pinna D, et al. Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine. J Clin Invest 2010;120:1663-73
19. Benjamin E, Wang W, McAuliffe JM, et al. A broadly neutralizing human monoclonal antibody directed against a novel conserved epitope on the influenza virus H3 hemagglutinin globular head. J Virol 2014;88:6743-50
20. Okuno Y, Isegawa Y, Sasao F, et al. A common neutralizing epitope conserved between the hemagglutinins of influenza A virus H1 and H2 strains. J Virol 1993;67:2552-8
21. Smirnov YA, Lipatov AS, Gitelman AK, et al. An epitope shared by the hemagglutinins of H1, H2, H5, and H6 subtypes of influenza A virus. Acta Virol 1999;43:237-44
22. Sui J, Hwang WC, Perez S, et al. Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat Struct Mol Biology 2009;16: 265-73
23. Throsby M, van den Brink E, Jongeneelen M, et al. Heterosubtypic neutralizing monoclonal antibodies cross-protective against H5N1 and H1N1 recovered from human IgM+ memory B cells. PLoS One 2008;3(12): e3942
24. Whittle JRR, Wheatley AK, Wu L, et al. Flow cytometry reveals that H5N1 vaccination elicits cross-reactive stemdirected antibodies from multiple Ig heavy-chain lineages. J Virol 2014;88: 4047-57
25. Wrammert J, Koutsonanos D, Li GM, et al. Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection. J Exp Med 2011;208:181-93
26. Dreyfus C, Ekiert DC, Wilson IA. Structure of a classical broadly neutralizing stem antibody in complex with a pandemic H2 influenza virus hemagglutinin. J Virol 2013;87:7149-54
27. Ekiert DC, Bhabha G, Elsliger MA, et al. Antibody recognition of a highly conserved influenza virus epitope. Science 2009;324: 246-51
28. Ekiert DC, Friesen RH, Bhabha G, et al. A highly conserved neutralizing epitope on group 2 influenza A viruses. Science 2011;333:843-50
29. Friesen RH, Lee PS, Stoop EJ, et al. A common solution to group 2 influenza virus neutralization. Proc Natl Acad Sci USA 2014;111:445-50
30. Tan GS, Lee PS, Hoffman RM, et al. Characterization of a broadly neutralizing monoclonal antibody that targets the fusion domain of group 2 influenza A virus hemagglutinin. J Virol 2014;88:13580-92
31. Corti D, Voss J, Gamblin SJ, et al. A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. Science 2011;333:850-6
32. Dreyfus C, Laursen NS, Kwaks T, et al. Highly conserved protective epitopes on influenza B viruses. Science 2012;337: 1343-8
33. Nakamura G, Chai N, Park S, et al. An in vivo human-plasmablast enrichment technique allows rapid identification of therapeutic influenza A antibodies. Cell Host Microbe 2013;14:93-103
34. Brandenburg B. Koudstaal W, Goudsmit J, et al. Mechanisms of Hemagglutinin Targeted Influenza Virus Neutralization. PLoS One 2013;8(12):e80034
35. DiLillo DJ, Tan GS, Palese P, et al. Broadly neutralizing hemagglutinin stalk-specific antibodies require FcgR interactions for protection against influenza virus in vivo. Nat Med 2014;20:143-51
36. Air G. M. Influenza virus antigenicity and broadly neutralizing epitopes. Current opinion in virology 2015;11:113-21
37. Tan G, Krammer F, Eggink D, et al. A pan-H1 anti-hemagglutinin monoclonal antibody with potent broad-spectrum efficacy in vivo. J Virol 2012;86:6179-88
38. Sui J, Sheehan J, Hwang WC, et al. Wide prevalence of heterosubtypic broadly neutralizing human anti-influenza A antibodies. Clin Infect Dis 2011;52: 1003-9
39. Margine I, Hai R, Albrecht RA, et al. H3N2 influenza virus infection induces broadly reactive hemagglutinin stalk antibodies in humans and mice. J Virol 2013;87:4728-37
40. Moody MA, Zhang R, Walter EB, et al. H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination. PLoS One 2011;6(10):e25797
41. Thomson CA, Wang Y, Jackson LM, et al. Pandemic H1N1 Influenza Infection and Vaccination in Humans Induces Cross-Protective Antibodies that Target the Hemagglutinin Stem. Front Immunol 2012;3:87
42. He XSS, Sasaki S, Baer J, et al. Heterovariant cross-reactive B-cell responses induced by the 2009 pandemic influenza virus A subtype H1N1 vaccine. J Infect Dis 2013;207:288-96
43. Jegaskanda S, Amarasena TH, Laurie KL, et al. Standard trivalent influenza virus protein vaccination does not prime antibody-dependent cellular cytotoxicity in macaques. J Virol 2013;87:13706-18
44. Giudice G, Hilbert A, Bugarini R, et al. An MF59-adjuvanted inactivated influenza vaccine containing A/Panama/1999 (H3N2) induced broader serological protection against heterovariant influenza virus strain A/Fujian/2002 than a subunit and a split influenza vaccine. Vaccine 2006;24(16): 3063-5
45. Orsi A, Ansaldi F, de Florentiis D, et al. Cross-protection against drifted influenza viruses: options offered by adjuvanted and intradermal vaccines. Human vaccines & immunotherapeutics 2013;9:582-90
46. Ansaldi F, Zancolli M, Durando P, et al. Antibody response against heterogeneous circulating influenza virus strains elicited by MF59- and non-adjuvanted vaccines during seasons with good or partial matching between vaccine strain and clinical isolates. Vaccine 2010;28:4123-9
47. Ansaldi F, Bacilieri S, Durando P, et al. Cross-protection by MF59-adjuvanted influenza vaccine: neutralizing and haemagglutination-inhibiting antibody activity against A(H3N2) drifted influenza viruses. Vaccine 2008;26(12):1525-9
48. Banzhoff A, Gasparini R, Laghi-Pasini F, et al. MF59-adjuvanted H5N1 vaccine induces immunologic memory and heterotypic antibody responses in non-elderly and elderly adults. PLoS One 2009;4(2):e4384
49. Alberini I, E, Del Tordello et al. Pseudoparticle neutralization is a reliable assay to measure immunity and cross-reactivity to H5N1 influenza viruses. Vaccine 2009;27:5998-6003
50. Even-Or O, Samira S, Ellis R, et al. Adjuvanted influenza vaccines. Expert Rev Vaccines 2013;12:1095-108
51. Wei CJJ, Boyington JC, McTamney PM, et al. Induction of broadly neutralizing H1N1 influenza antibodies by vaccination. Science 2010;329:1060-4
52. Kanekiyo M, Wei JJ, Yassine HM, et al. Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies. Nature 2013;499:102-6
53. Chen MWW, Cheng RJ, Huang Y, et al. A consensus-hemagglutinin-based DNA vaccine that protects mice against divergent H5N1 influenza viruses. Proc Natl Acad Sci USA 2008;105:13538-43
54. Weaver EA, Rubrum AM, Webby RJ, Barry MA. Protection against divergent influenza H1N1 virus by a centralized influenza hemagglutinin. PLoS One 2011; 6(3):e18314
55. Yan J, Villarreal DO, Racine T, et al. Protective immunity to H7N9 influenza viruses elicited by synthetic DNA vaccine. Vaccine 2014;32:2833-42
56. Giles BM, Ross TM. A computationally optimized broadly reactive antigen (COBRA) based H5N1 VLP vaccine elicits broadly reactive antibodies in mice and ferrets. Vaccine 2011;29:3043-54
57. Giles BM, Bissel SJ, Dealmeida DR, et al. Ross. Antibody breadth and protective efficacy are increased by vaccination with computationally optimized hemagglutinin but not with polyvalent hemagglutinin-based H5N1 virus-like particle vaccines. Clin Vaccine Immunol 2012;19:128-39
58. Giles BM, Crevar CJ, Carter DM, et al. A computationally optimized hemagglutinin virus-like particle vaccine elicits broadly reactive antibodies that protect nonhuman primates from H5N1 infection. J Infect Dis 2012;205:1562-70
59. Graves PN, Schulman JL, Young JF, Palese P. Preparation of influenza virus subviral particles lacking the HA1 subunit of hemagglutinin: unmasking of cross-reactive HA2 determinants. Virology 1983;126:106-16
60. Sagawa H, Ohshima A, Kato I, et al. The immunological activity of a deletion mutant of influenza virus haemagglutinin lacking the globular region. J Gen Virol 1996; 77(7):1483-7
61. Steel J, Lowen AC, Wang TT, et al. Influenza virus vaccine based on the conserved hemagglutinin stalk domain. mBio 2010;1(1):e00018-0
62. Bommakanti G, Lu X, Citron MP, et al. Design of Escherichia coli-expressed stalk domain immunogens of H1n1 hemagglutinin that protect mice from lethal challenge. J Virol 2012;86(24):13434-44
63. Bommakanti G, Citron MP, Hepler RW, et al. Design of an HA2-based Escherichia coli expressed influenza immunogen that protects mice from pathogenic challenge. Proc Natl Acad Sci USA 2010;107(31): 13701-6
64. Mallajosyula VVA, Citron MP, Ferrara F, et al. Influenza hemagglutinin stem-fragment immunogen elicits broadly neutralizing antibodies and confers heterologous protection. Proc Natl Acad Sci USA 2014;111(25):E2514-23
65. Lu Y, Welsh JP, Swartz JR. Production and stabilization of the trimeric influenza hemagglutinin stem domain for potentially broadly protective influenza vaccines. Proc Natl Acad Sci USA 2014;11(1):125-30
66. Pica N, Hai R, Krammer F, et al. Hemagglutinin stalk antibodies elicited by the 2009 pandemic influenza virus as a mechanism for the extinction of seasonal H1N1 viruses. Proc Natl Acad Sci USA 2012;109:2573-8
67. Ellebedy AH, Krammer F, Li GM, et al. Induction of broadly cross-reactive antibody responses to the influenza HA stem region following H5N1 vaccination in humans. Proc Natl Acad Sci USA 2014;111:13133-8
68. Nachbagauer R, Wohlbold TJ, Hirsh A, et al. Induction of broadly reactive anti-hemagglutinin stalk antibodies by an H5N1 vaccine in humans. J Virol 2014;88: 13260-8
69. Ledgerwood JE, Zephir K, Hu Z, et al. Prime-boost interval matters: a randomized phase 1 study to identify the minimum interval necessary to observe the H5 DNA influenza vaccine priming effect. J Infect Dis 2013;208:418-22
70. Wheatley AK, Whittle JR, Lingwood D, et al. H5N1 Vaccine-Elicited Memory B Cells Are Genetically Constrained by the IGHV Locus in the Recognition of a Neutralizing Epitope in the Hemagglutinin Stem. J Immunol 2015;195(2):602-10
71. Miller MS, Tsibane T, Krammer F, et al. 1976 and 2009 H1N1 influenza virus vaccines boost anti-hemagglutinin stalk antibodies in humans. J Infect Dis 2013;207:98-105
72. Li GM, Chiu C, Wrammert J, et al. Pandemic H1N1 influenza vaccine induces a recall response in humans that favors broadly cross-reactive memory B cells. Proc Natl Acad Sci USA 2012;109:9047-52
73. Krammer F, Palese P. Universal influenza virus vaccines: need for clinical trials. Nature immunology 2014;15:3-5
74. Krammer F, Palese P. Advances in the development of influenza virus vaccines. Nat Rev Drug Discov 2015;14:167-82
75. Hai R, Krammer F, Tan GS, et al. Influenza viruses expressing chimeric hemagglutinins: globular head and stalk domains derived from different subtypes. J Virol 2012;86:5774-81
76. Krammer F, Hai R, Yondola M, et al. Assessment of influenza virus hemagglutinin stalk-based immunity in ferrets. J Virol 2014;88:3432-42
77. Krammer F, Pica N, Hai R, et al. Chimeric hemagglutinin influenza virus vaccine constructs elicit broadly protective stalk-specific antibodies. J Virol 2013;87: 6542-50
78. Krammer F, Margine I, Hai R, et al. H3 stalk-based chimeric hemagglutinin influenza virus constructs protect mice from H7N9 challenge. J Virol 2014;88:2340-3
79. Margine I, Krammer F, Hai R, et al. Hemagglutinin stalk-based universal vaccine constructs protect against group 2 influenza A viruses. J Virol 2013;87:10435-46
80. Lin SCC, Liu C, Jan T, Wu SCC. Glycan masking of hemagglutinin for adenovirus vector and recombinant protein immunizations elicits broadly neutralizing antibodies against H5N1 avian influenza viruses. PLoS One 2014;9(3):e92822
81. Lin S-C, Lin YF, Chong P, Wu SC. Broader neutralizing antibodies against H5N1 viruses using prime-boost immunization of hyperglycosylated hemagglutinin DNA and virus-like particles. PLoS One 2012;7(6):e39075
82. Wang TT, Tan GS, Hai R, et al. Broadly protective monoclonal antibodies against H3 influenza viruses following sequential immunization with different hemagglutinins. PLoS Pathog 2010;6(2):e1000796
83. Deng L, Cho KJ, Fiers W, Saelens X. M2e-based universal influenza A vaccines. Vaccines 2015;3:105-36
84. Zhang N, Zheng J, Lu L, et al. Advancements in the development of subunit influenza vaccines. Microbes Infect 2015;17:123-34
85. Zheng M, Luo J, Chen Z. Development of universal influenza vaccines based on influenza virus M and NP genes. Infection 2014;42:251-62
86. Schotsaert M, De Filette M, Fiers W, Saelens X. Universal M2 ectodomain-based influenza A vaccines: preclinical and clinical developments. Expert Rev Vaccines 2009;8: 499-508
87. Liu X, Guo J, Han S, et al. Enhanced immune response induced by a potential influenza A vaccine based on branched M2e polypeptides linked to tuftsin. Vaccine 2012;30:6527-33
88. Huleatt JW, Nakaar V, Desai P, et al. Potent immunogenicity and efficacy of a universal influenza vaccine candidate comprising a recombinant fusion protein linking influenza M2e to the TLR5 ligand flagellin. Vaccine 2008;26:201-14
89. Neirynck S, Deroo T, Saelens X, et al. A universal influenza A vaccine based on the extracellular domain of the M2 protein. Nat Med 1999;5:1157-63
90. Muto NA, Yoshida R, Suzuki T, et al. Inhibitory effects of an M2-specific monoclonal antibody on different strains of influenza A virus. Jpn J Vet Res 2012;60: 71-83
91. Kim MCC, Lee JS, Kwon M, et al. Multiple heterologous M2 extracellular domains presented on virus-like particles confer broader and stronger M2 immunity than live influenza A virus infection. Antiviral Res 2013;99:328-35
92. El Bakkouri K, Descamps F, De Filette M, et al. Universal vaccine based on ectodomain of matrix protein 2 of influenza A: Fc receptors and alveolar macrophages mediate protection. J Immunol 2011;186: 1022-31
93. Grandea AG III, Olsen OA, Cox TC, et al. Human antibodies reveal a protective epitope that is highly conserved among human and nonhuman influenza A viruses. Proc Natl Acad Sci USA 2010;107: 12658-63
94. Treanor JJ, Tierney EL, Zebedee SL, et al. Passively transferred monoclonal antibody to the M2 protein inhibits influenza A virus replication in mice. J Virol 1990;64:1375-7
95. Song A, Myojo K, Laudenslager J, et al. Evaluation of a fully human monoclonal antibody against multiple influenza A viral strains in mice and a pandemic H1N1 strain in nonhuman primates. Antiviral Res 2014;111:60-8
96. Wang R, Song A, Levin J, et al. Therapeutic potential of a fully human monoclonal antibody against influenza A virus M2 protein. Antiviral Res 2008;80: 168-77
97. Stepanova LA, Kotlyarov RY, Kovaleva AA, et al. Protection against Multiple Influenza A Virus Strains Induced by Candidate Recombinant Vaccine Based on Heterologous M2e Peptides Linked to Flagellin. PLoS One 2015;10:e0119520
98. Ramos EL, Mitcham JL, Koller TD, et al. Efficacy and safety of treatment with an anti-m2e monoclonal antibody in experimental human influenza. J Infect Dis 2015;211:1038-44
99. Turley CB, Rupp RE, Johnson C, et al. Safety and immunogenicity of a recombinant M2e-flagellin influenza vaccine (STF2.4xM2e) in healthy adults. Vaccine 2011;29:5145-52
100. Talbot HK, Michael TR, Casey J, et al. Immunopotentiation of trivalent influenza vaccine when given with VAX102, a recombinant influenza M2e vaccine fused to the TLR5 ligand flagellin. PLoS One 2010; 5(12):e14442
101. Antrobus RD, Lillie PJ, Berthoud TK, et al. A T cell-inducing influenza vaccine for the elderly: safety and immunogenicity of MVA-NP+M1 in adults aged over 50 years. PLoS One 2012;7:e48322
102. Sandbulte MR, Jimenez GS, Boon AC, et al. Cross-reactive neuraminidase antibodies afford partial protection against H5N1 in mice and are present in unexposed humans. PLoS Med 2007;4(2):e59
103. Wan H, Yang H, Shore DA, et al. Structural characterization of a protective epitope spanning A(H1N1)pdm09 influenza virus neuraminidase monomers. Nature communications 2015;6:6114
104. Gravel C, Li C, Wang J, et al. Quantitative analyses of all influenza type A viral hemagglutinins and neuraminidases using universal antibodies in simple slot blot assays. J Vis Exp 2011;50:2784
105. Gui X, Ge P, Wang X, et al. Identification of a highly conserved and surface exposed B-cell epitope on the nucleoprotein of influenza A virus. J Med Virol 2014;86: 995-1002
106. Wan H, Gao J, Xu K, et al. Molecular basis for broad neuraminidase immunity: conserved epitopes in seasonal and pandemic H1N1 as well as H5N1 influenza viruses. J Virol 2013;87:9290-300
107. Couch RB, Atmar RL, Keitel WA, et al. Randomized comparative study of the serum antihemagglutinin and antineuraminidase antibody responses to six licensed trivalent influenza vaccines. Vaccine 2012;31:190-5
108. Kilbourne ED, Couch RB, Kasel JA, et al. Purified influenza A virus N2 neuraminidase vaccine is immunogenic and non-toxic in humans. Vaccine 1995;13:1799-803
109. Jegaskanda S, Reading PC, Kent SJ. Influenza-specific antibody-dependent cellular cytotoxicity: toward a universal influenza vaccine. J Immunol 2014;193: 469-75
110. Sridhar S, Begom S, Bermingham A, et al. Cellular immune correlates of protection against symptomatic pandemic influenza. Nat Med 2013;19:1305-12
111. Hayward AC, Wang L, Goonetilleke N, et al. Natural T Cell-mediated Protection against Seasonal and Pandemic Influenza. Results of the Flu Watch Cohort Study. Am J Respire Crit Care Med 2015;191:1422-31
112. Price GE, Soboleski MR, Lo Y, et al. Vaccination focusing immunity on conserved antigens protects mice and ferrets against virulent H1N1 and H5N1 influenza A viruses. Vaccine 2009;27:6512-21
113. Rao SS, Kong P, Wei J, et al. Comparative efficacy of hemagglutinin, nucleoprotein, and matrix 2 protein gene-based vaccination against H5N1 influenza in mouse and ferret. PLoS One 2010;5(3):e9812
114. Francis T. On the doctrine of original antigenic sin. Proc Am Philos Soc 1960;104:572-8
115. Fazekas de St G, Webster RG. Disquisitions on Original Antigenic Sin. II. Proof in lower creatures. J Exp Med 1966;124: 347-61
116. Fazekas de St G, Webster RG. Disquisitions of Original Antigenic Sin. I. Evidence in man. J Exp Med 1966;124:331-45
117. Lessler J, Riley S, Read JM, et al. Evidence for antigenic seniority in influenza A (H3N2) antibody responses in southern China. PLoS Pathog 2012;8(7):e1002802
118. Miller MS, Gardner TJ, Krammer F, et al. Neutralizing antibodies against previously encountered influenza virus strains increase over time: a longitudinal analysis. Sci Transl Med 2013;5(198):198ra107
119. Davenport FM, Hennessy AV, Francis T. Epidemiologic and immunologic significance of age distribution of antibody to antigenic variants of influenza virus. J Exp Med 1953;98:641-56
120. Andrews SF, Kaur K, Pauli NT, et al. High preexisting serological antibody levels correlate with diversification of the influenza vaccine response. J Virol 2015;89:3308-17
121. Sasaki S, He SXS, Holmes TH, et al. Influence of prior influenza vaccination on antibody and B-cell responses. PLoS One 2008;3(8):e2975
122. Bodewes R, de Mutsert G, van der Klis FR, et al. Prevalence of antibodies against seasonal influenza A and B viruses in children in Netherlands. Clin Vaccine Immunol 2011;18:469-76
123. Kucharski AJ, Lessler J, Read JM, et al. Estimating the life course of influenza A (H3N2) antibody responses from cross-sectional data. PLoS Biol 2015;13(3): e1002082
124. Steel J, Staeheli P, Mubareka S, et al. Transmission of pandemic H1N1 influenza virus and impact of prior exposure to seasonal strains or interferon treatment. J Virol 2010;84:21-6
125. Min JY, Chen GL, Santos C, et al. Classical swine H1N1 influenza viruses confer cross protection from swine-origin 2009 pandemic H1N1 influenza virus infection in mice and ferrets. Virology 2010;408:128-33
126. O'Donnell CD, Wright A, Vogel LN, et al. Effect of priming with H1N1 influenza viruses of variable antigenic distances on challenge with 2009 pandemic H1N1 virus. J Virol 2012;86:8625-33
127. Carter DM, Bloom CE, Nascimento EJ, et al. Sequential seasonal H1N1 influenza virus infections protect ferrets against novel 2009 H1N1 influenza virus. J Virol 2013;87:1400-10
128. Wei CJJ, Yassine HM, McTamney PM, et al. Elicitation of broadly neutralizing influenza antibodies in animals with previous influenza exposure. Sci Transl Med 2012;4(147):147ra114
129. Del Giudice G, Stittelaar KJ, van Amerongen G, et al. Seasonal influenza vaccine provides priming for A/H1N1 immunization. Sci Transl Med 2009;1(12):12re1
130. Kuiken T, Rimmelzwaan GF, Van Amerongen G, Osterhaus AD. Pathology of human influenza A (H5N1) virus infection in cynomolgus macaques (Macaca fascicularis). Vet Pathol 2003;40: 304-10
131. O'Donnell CD, Subbarao K. The contribution of animal models to the understanding of the host range and virulence of influenza A viruses. Microbes Infect 2011;13:502-15
132. Sundling C, Phad G, Douagi I, et al. Isolation of antibody V(D)J sequences from single cell sorted rhesus macaque B cells. J Immunol Methods 2012;386:85-93
133. Hogarth PM, Anania JC, Wines BD. The FcgR of humans and non-human primates and their interaction with IgG: implications for induction of inflammation, resistance to infection and the use of therapeutic monoclonal antibodies. Curr Top Micrbiol Immunol 2014;382:321-52
134. Weinfurter JT, Brunner K, Capuano SV III, et al. Cross-reactive T cells are involved in rapid clearance of 2009 pandemic H1N1 influenza virus in nonhuman primates. PLoS pathogens 2011;7:e1002381
135. Jegaskanda S, Weinfurter JT, Friedrich TC, Kent SJ. Antibody-dependent cellular cytotoxicity is associated with control of pandemic H1N1 influenza virus infection of macaques. J Virol 2013;87:5512-22
136. Yu X, Tsibane T, McGraw PA, et al. Neutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors. Nature 2008;455:532-6
137. Dormitzer PR, Galli G, Castellino F, et al. Influenza vaccine immunology. Immunol Rev 2011;239:167-77
138. Jiang N, He J, Weinstein JA, et al. Lineage structure of the human antibody repertoire in response to influenza vaccination. Sci Transl Med 2013;5:171ra119
139. Victora GD, Nussenzweig MC. Germinal centers. Annu Rev Immunol 2012;30: 429-57
140. Nayak JL, Fitzgerald TF, Richards KA, et al. CD4+ T-cell expansion predicts neutralizing antibody responses to monovalent, inactivated 2009 pandemic influenza A(H1N1) virus subtype H1N1 vaccine. J Infect Dis 2013;207: 297-305
141. Bentebibel SE, Lopez S, Obermoser G, et al. Induction of ICOS+CXCR3+CXCR5+ TH cells correlates with antibody responses to influenza vaccination. Sci Transl Med 2013;5:176ra132
142. Richards KA, Nayak J, Chaves FA, et al. Seasonal Influenza Can Poise Hosts for CD4 T-Cell Immunity to H7N9 Avian Influenza. J Infect Dis 2014;212(1):86-94
143. Ge X, Tan V, Bollyky PL, et al. Assessment of seasonal influenza A virus-specific CD4 T-cell responses to 2009 pandemic H1N1 swine-origin influenza A virus. J Virol 2010;84:3312-19
144. Richards KA, Topham D, Chaves FA, Sant AJ. Cutting edge: CD4 T cells generated from encounter with seasonal influenza viruses and vaccines have broad protein specificity and can directly recognize naturally generated epitopes derived from the live pandemic H1N1 virus. J Immunol 2010;185:4998-5002
145. Evaluation of the Protective Efficacy and Safety of CR8020 in an Influenza Challenge. Available from: https://clinicaltrials.gov/ct2/show/NCT01938352
146. Study in Healthy Volunteers to Evaluate the Efficacy and Safety of CR6261 in an H1N1 Influenza Healthy Human Challenge Model. Available from:https://clinicaltrials.gov/ct2/show/NCT02371668
147. A Study of MHAA4549A in Healthy Volunteers in an Influenza Challenge Model. Available from: https://clinicaltrials.gov/ct2/show/NCT01980966 [Last accessed 3 March 2015]
148. Khurana S, Loving CL, Manischewitz J, et al. Vaccine-induced anti-HA2 antibodies promote virus fusion and enhance influenza virus respiratory disease. Sci Transl Med 2013;5(200):200ra114
149. Gamblin SJ, Haire LF, Russell RJ, et al. The structure and receptor binding properties of the 1918 influenza hemagglutinin. Science 2004;303(5665): 1838-42