Universal immunity to influenza must outwit immune evasion

Frontiers in Microbiology

Volumn 5, Issue JUN, 2014, Pages

  Quiñones Parra, Sergio ^a   Loh, Liyen ^a   Brown, Lorena E ^a   Kedzierska, Katherine ^a   Valkenburg, Sophie A ^b  

^a UNIVERSITY OF MELBOURNE   (Australia)

^b UNIVERSITY OF HONG KONG   (Hong Kong)

Author keywords

Antibodies; Influenza viruses; T cells memory; Vaccine design; Viral escape mechanisms

Indexed keywords

ANTIBODY RESPONSE; CD8+ T LYMPHOCYTE; CROSS REACTION; CYTOKINE PRODUCTION; CYTOTOXICITY; DISEASE SEVERITY; HEMAGGLUTINATION INHIBITION TEST; HUMAN; IMMUNE EVASION; IMMUNIZATION; INFLUENZA; INFLUENZA A (H1N1); INFLUENZA VIRUS A H2N2; INFLUENZA VIRUS A H3N2; INFLUENZA VIRUS A H5N1; INFLUENZA VIRUS A H7N9; MEMORY T LYMPHOCYTE; NONHUMAN; PHYLOGENY; REVIEW; VIRUS NEUTRALIZATION;

EID: 84905171266     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2014.00285     Document Type: Review

References (121)

1. Akondy, R. S., Monson, N. D., Miller, J. D., Edupuganti, S., Teuwen, D., Wu, H., et al. (2009). The yellow fever virus vaccine induces a broad and polyfunctional human memory CD8+ T cell response. J. Immunol. 183, 7919-7930. doi: 10.4049/jimmunol.0803903
2. Allan, W., Tabi, Z., Cleary, A., and Doherty, P. C. (1990). Cellular events in the lymph node and lung of mice with influenza. Consequences of depleting CD4+ T cells. J. Immunol. 144, 3980-3986.
3. Antrobus, R. D., Lillie, P. J., Berthoud, T. K., Spencer, A. J., McLaren, J. E., Ladell, K., et al. (2012). A T cell-inducing influenza vaccine for the elderly: safety and immunogenicity of MVA-NP+M1 in adults aged over 50 years. PLoS ONE 7:e48322. doi: 10.1371/journal.pone.0048322
4. Askonas, B. A., Taylor, P. M., and Esquivel, F. (1988). Cytotoxic T cells in influenza infection. Ann. N.Y. Acad. Sci. 532, 230-237. doi: 10.1111/j.1749-6632.1988.tb36342.x
5. Assarsson, E., Bui, H. H., Sidney, J., Zhang, Q., Glenn, J., Oseroff, C., et al. (2008). Immunomic analysis of the repertoire of T-cell specificities for influenza A virus in humans. J. Virol. 82, 12241-12251. doi: 10.1128/JVI.01563-08
6. Belz, G. T., Wodarz, D., Diaz, G., Nowak, M. A., and Doherty, P. C. (2002). Compromised influenza virus-specific CD8(+)-T-cell memory in CD4(+)-T-cell-deficient mice. J. Virol. 76, 12388-12393. doi: 10.1128/JVI.76.23.12388-12393.2002
7. Bender, B. S., Croghan, T., Zhang, L., and Small, P. A. Jr. (1992). Transgenic mice lacking class I major histocompatibility complex-restricted T cells have delayed viral clearance and increased mortality after influenza virus challenge. J. Exp. Med. 175, 1143-1145. doi: 10.1084/jem.175.4.1143
8. Bentebibel, S. E., Lopez, S., Obermoser, G., Schmitt, N., Mueller, C., Harrod, C., et al. (2013). Induction of ICOS+CXCR3+CXCR5+ TH cells correlates with antibody responses to influenza vaccination. Sci. Transl. Med. 5:176ra132. doi: 10.1126/scitranslmed.3005191
9. Berkhoff, E. G., De Wit, E., Geelhoed-Mieras, M. M., Boon, A. C., Symons, J., Fouchier, R. A., et al. (2005). Functional constraints of influenza A virus epitopes limit escape from cytotoxic T lymphocytes. J. Virol. 79, 11239-11246. doi: 10.1128/JVI.79.17.11239-11246.2005
10. Berthoud, T. K., Hamill, M., Lillie, P. J., Hwenda, L., Collins, K. A., Ewer, K. J., et al. (2011). Potent CD8+ T-cell immunogenicity in humans of a novel heterosubtypic influenza A vaccine, MVA-NP+M1. Clin. Infect. Dis. 52, 1-7. doi: 10.1093/cid/ciq015
11. Berzins, S. P., Smyth, M. J., and Baxter, A. G. (2011). Presumed guilty: natural killer T cell defects and human disease. Nat. Rev. Immunol. 11, 131-142. doi: 10.1038/nri2904
12. Bodewes, R., Fraaij, P. L., Geelhoed-Mieras, M. M., Van Baalen, C. A., Tiddens, H. A., Van Rossum, A. M., et al. (2011). Annual vaccination against influenza virus hampers development of virus-specific CD8(+) T cell immunity in children. J. Virol. 85, 11995-12000. doi: 10.1128/JVI.05213-11
13. Bodewes, R., Kreijtz, J. H., Hillaire, M. L., Geelhoed-Mieras, M. M., Fouchier, R. A., Osterhaus, A. D., et al. (2010). Vaccination with whole inactivated virus vaccine affects the induction of heterosubtypic immunity against influenza virus A/H5N1 and immunodominance of virus-specific CD8+ T-cell responses in mice. J. Gen. Virol. 91, 1743-1753. doi: 10.1099/vir.0.020784-0
14. Boon, A. C., De Mutsert, G., Van Baarle, D., Smith, D. J., Lapedes, A. S., Fouchier, R. A., et al. (2004). Recognition of homo- and heterosubtypic variants of influenza A viruses by human CD8+ T lymphocytes. J. Immunol. 172, 2453-2460. doi: 10.4049/jimmunol.172.4.2453
15. Born, W. K., Kemal Aydintug, M., and O'Brien, R. L. (2013). Diversity of gammadelta T-cell antigens. Cell. Mol. Immunol. 10, 13-20. doi: 10.1038/cmi.2012.45
16. Braciale, T. J. (1977). Immunologic recognition of influenza virus-infected cells. II. Expression of influenza A matrix protein on the infected cell surface and its role in recognition by cross-reactive cytotoxic T cells. J. Exp. Med. 146, 673-689. doi: 10.1084/jem.146.3.673
17. Carragher, D. M., Kaminski, D. A., Moquin, A., Hartson, L., and Randall, T. D. (2008). A novel role for non-neutralizing antibodies against nucleoprotein in facilitating resistance to influenza virus. J. Immunol. 181, 4168-4176. doi: 10.4049/jimmunol.181.6.4168
18. Christensen, J. P., Doherty, P. C., Branum, K. C., and Riberdy, J. M. (2000). Profound protection against respiratory challenge with a lethal H7N7 influenza A virus by increasing the magnitude of CD8(+) T-cell memory. J. Virol. 74, 11690-11696. doi: 10.1128/JVI.74.24.11690-11696.2000
19. Chua, B. Y., Olson, M. R., Bedoui, S., Sekiya, T., Wong, C. Y., Turner, S. J., et al. (2014). The use of a TLR2 agonist-based adjuvant for enhancing effector and memory CD8 T-cell responses. Immunol. Cell Biol. 92, 377-383. doi: 10.1038/icb.2013.102
20. Chua, B. Y., Pejoski, D., Turner, S. J., Zeng, W., and Jackson, D. C. (2011). Soluble proteins induce strong CD8+ T cell and antibody responses through electrostatic association with simple cationic or anionic lipopeptides that target TLR2. J. Immunol. 187, 1692-1701. doi: 10.4049/jimmunol.1100486
21. Corti, D., and Lanzavecchia, A. (2013). Broadly neutralizing antiviral antibodies. Annu. Rev. Immunol. 31, 705-742. doi: 10.1146/annurev-immunol-032712-095916
22. Corti, D., Suguitan, A. L. Jr., Pinna, D., Silacci, C., Fernandez-Rodriguez, B. M., Vanzetta, F., et al. (2010). Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine. J. Clin. Invest. 120, 1663-1673. doi: 10.1172/JCI41902
23. Corti, D., Voss, J., Gamblin, S. J., Codoni, G., Macagno, A., Jarrossay, D., et al. (2011). A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. Science 333, 850-856. doi: 10.1126/science.1205669
24. Cosgrove, C., Ussher, J. E., Rauch, A., Gartner, K., Kurioka, A., Huhn, M. H., et al. (2013). Early and nonreversible decrease of CD161++ /MAIT cells in HIV infection. Blood 121, 951-961. doi: 10.1182/blood-2012-06-436436
25. DiLillo, D. J., Tan, G. S., Palese, P., and Ravetch, J. V. (2014). Broadly neutralizing hemagglutinin stalk-specific antibodies require FcgammaR interactions for protection against influenza virus in vivo. Nat. Med. 20, 143-151. doi: 10.1038/nm.3443
26. Dougan, S. K., Ashour, J., Karssemeijer, R. A., Popp, M. W., Avalos, A. M., Barisa, M., et al. (2013). Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus. Nature 503, 406-409. doi: 10.1038/nature12637
27. Dreyfus, C., Laursen, N. S., Kwaks, T., Zuijdgeest, D., Khayat, R., Ekiert, D. C., et al. (2012). Highly conserved protective epitopes on influenza B viruses. Science 337, 1343-1348. doi: 10.1126/science.1222908
28. Eichelberger, M. C., Wang, M. L., Allan, W., Webster, R. G., and Doherty, P. C. (1991). Influenza virus RNA in the lung and lymphoid tissue of immunologically intact and CD4-depleted mice. J. Gen. Virol. 72(pt 7), 1695-1698. doi: 10.1099/0022-1317-72-7-1695
29. Ekiert, D. C., Bhabha, G., Elsliger, M. A., Friesen, R. H., Jongeneelen, M., Throsby, M., et al. (2009). Antibody recognition of a highly conserved influenza virus epitope. Science 324, 246-251. doi: 10.1126/science.1171491
30. Ekiert, D. C., Friesen, R. H., Bhabha, G., Kwaks, T., Jongeneelen, M., Yu, W., et al. (2011). A highly conserved neutralizing epitope on group 2 influenza A viruses. Science 333, 843-850. doi: 10.1126/science.1204839
31. Ekiert, D. C., Kashyap, A. K., Steel, J., Rubrum, A., Bhabha, G., Khayat, R., et al. (2012). Cross-neutralization of influenza A viruses mediated by a single antibody loop. Nature 489, 526-532. doi: 10.1038/nature11414
32. Elhefnawi, M., Alaidi, O., Mohamed, N., Kamar, M., El-Azab, I., Zada, S., et al. (2011). Identification of novel conserved functional motifs across most Influenza A viral strains. Virol. J. 8:44. doi: 10.1186/1743-422X-8-44
33. Epstein, S. L. (2006). Prior H1N1 influenza infection and susceptibility of Cleveland Family Study participants during the H2N2 pandemic of 1957: an experiment of nature. J. Infect. Dis. 193, 49-53. doi: 10.1086/498980
34. Epstein, S. L., Kong, W. P., Misplon, J. A., Lo, C. Y., Tumpey, T. M., Xu, L., et al. (2005). Protection against multiple influenza A subtypes by vaccination with highly conserved nucleoprotein. Vaccine 23, 5404-5410. doi: 10.1016/j.vaccine.2005.04.047
35. Epstein, S. L., Lo, C. Y., Misplon, J. A., and Bennink, J. R. (1998). Mechanism of protective immunity against influenza virus infection in mice without antibodies. J. Immunol. 160, 322-327.
36. Fernandez, C., Stratov, I., De Rose, R., Walsh, K., Dale, C., Smith, M., et al. (2005). Rapid viral escape at an immunodominant simian-human immunodeficiency virus cytotoxic T-lymphocyte epitope exacts a dramatic fitness cost. J. Virol. 79, 5721-5731. doi: 10.1128/JVI.79.9.5721-5731.2005
37. Flynn, K. J., Belz, G. T., Altman, J. D., Ahmed, R., Woodland, D. L., and Doherty, P. C. (1998). Virus-specific CD8+ T cells in primary and secondary influenza pneumonia. Immunity 8, 683-691. doi: 10.1016/S1074-7613(00)80573-7
38. Flynn, K. J., Riberdy, J. M., Christensen, J. P., Altman, J. D., and Doherty, P. C. (1999). In vivo proliferation of naive and memory influenza-specific CD8(+) T cells. Proc. Natl. Acad. Sci. U.S.A. 96, 8597-8602. doi: 10.1073/pnas.96.15.8597
39. Forrest, B. D., Pride, M. W., Dunning, A. J., Capeding, M. R., Chotpitayasunondh, T., Tam, J. S., et al. (2008). Correlation of cellular immune responses with protection against culture-confirmed influenza virus in young children. Clin. Vaccine Immunol. 15, 1042-1053. doi: 10.1128/CVI.00397-07
40. Fox, A., Le, N. M., Horby, P., Van Doorn, H. R., Nguyen, V. T., Nguyen, H. H., et al. (2012). Severe pandemic H1N1 2009 infection is associated with transient NK and T deficiency and aberrant CD8 responses. PLoS One 7:e31535. doi: 10.1371/journal.pone.0031535
41. Fu, T. M., Guan, L., Friedman, A., Schofield, T. L., Ulmer, J. B., Liu, M. A., et al. (1999). Dose dependence of CTL precursor frequency induced by a DNA vaccine and correlation with protective immunity against influenza virus challenge. J. Immunol. 162, 4163-4170.
42. Gog, J., Rimmelzwaan, G., Osterhaus, A., and Grenfell, B. (2003). Population dynamics of rapid fixation in cytotoxic T lymphocyte escape mutants of influenza A. Proc. Natl. Acad. Sci. U.S.A. 100, 11143-11147. doi: 10.1073/pnas.1830296100
43. Gorski, S. A., Hahn, Y. S., and Braciale, T. J. (2013). Group 2 innate lymphoid cell production of IL-5 is regulated by NKT cells during influenza virus infection. PLoS Pathog. 9:e1003615. doi: 10.1371/journal.ppat.1003615
44. Gotch, F., Mcmichael, A., and Rothbard, J. (1988). Recognition of influenza A matrix protein by HLA-A2-restricted cytotoxic T lymphocytes. Use of analogues to orientate the matrix peptide in the HLA-A2 binding site. J. Exp. Med. 168, 2045-2057. doi: 10.1084/jem.168.6.2045
45. Graham, M. B., and Braciale, T. J. (1997). Resistance to and recovery from lethal influenza virus infection in B lymphocyte-deficient mice. J. Exp. Med. 186, 2063-2068. doi: 10.1084/jem.186.12.2063
46. Grant, E., Wu, C., Chan, K. F., Eckle, S., Bharadwaj, M., Zou, Q. M., et al. (2013). Nucleoprotein of influenza A virus is a major target of immunodominant CD8+ T-cell responses. Immunol. Cell Biol. 91, 184-194. doi: 10.1038/icb.2012.78
47. Gras, S., Kedzierski, L., Valkenburg, S. A., Laurie, K., Liu, Y. C., Denholm, J. T., et al. (2010). Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses. Proc. Natl. Acad. Sci. U.S.A. 107, 12599-12604. doi: 10.1073/pnas.1007270107
48. Graves, P. N., Schulman, J. L., Young, J. F., and Palese, P. (1983). Preparation of influenza virus subviral particles lacking the HA1 subunit of hemagglutinin: unmasking of cross-reactive HA2 determinants. Virology 126, 106-116. doi: 10.1016/0042-6822(83)90465-8
49. Greenbaum, J. A., Kotturi, M. F., Kim, Y., Oseroff, C., Vaughan, K., Salimi, N., et al. (2009). Pre-existing immunity against swine-origin H1N1 influenza viruses in the general human population. Proc. Natl. Acad. Sci. U.S.A. 106, 20365-20370. doi: 10.1073/pnas.0911580106
50. Guillonneau, C., Mintern, J. D., Hubert, F. X., Hurt, A. C., Besra, G. S., Porcelli, S., et al. (2009). Combined NKT cell activation and influenza virus vaccination boosts memory CTL generation and protective immunity. Proc. Natl. Acad. Sci. U.S.A. 106, 3330-3335. doi: 10.1073/pnas.0813309106
51. Hamada, H., Bassity, E., Flies, A., Strutt, T. M., Garcia-Hernandez Mde, L., McKinstry, K. K., et al. (2013). Multiple redundant effector mechanisms of CD8+ T cells protect against influenza infection. J. Immunol. 190, 296-306. doi: 10.4049/jimmunol.1200571
52. He, X. S., Holmes, T. H., Zhang, C., Mahmood, K., Kemble, G. W., Lewis, D. B., et al. (2006). Cellular immune responses in children and adults receiving inactivated or live attenuated influenza vaccines. J. Virol. 80, 11756-11766. doi: 10.1128/JVI.01460-06
53. Hillaire, M. L., Vogelzang-Van Trierum, S. E., Kreijtz, J. H., De Mutsert, G., Fouchier, R. A., Osterhaus, A. D., et al. (2013). Human T-cells directed to seasonal influenza A virus cross-react with 2009 pandemic influenza A (H1N1) and swine-origin triple-reassortant H3N2 influenza viruses. J. Gen. Virol. 94, 583-592. doi: 10.1099/vir.0.048652-0
54. Isakova-Sivak, I., Chen, L. M., Matsuoka, Y., Voeten, J. T., Kiseleva, I., Heldens, J. G., et al. (2011). Genetic bases of the temperature-sensitive phenotype of a master donor virus used in live attenuated influenza vaccines: A/Leningrad/134/17/57 (H2N2). Virology 412, 297-305. doi: 10.1016/j.virol.2011.01.004
55. Jegaskanda, S., Amarasena, T. H., Laurie, K. L., Tan, H. X., Butler, J., Parsons, M. S., et al. (2013a). Standard trivalent influenza virus protein vaccination does not prime antibody-dependent cellular cytotoxicity in macaques. J. Virol. 87, 13706-13718. doi: 10.1128/JVI.01666-13
56. Jegaskanda, S., Job, E. R., Kramski, M., Laurie, K., Isitman, G., De Rose, R., et al. (2013b). Cross-reactive influenza-specific antibody-dependent cellular cytotoxicity antibodies in the absence of neutralizing antibodies. J. Immunol. 190, 1837-1848. doi: 10.4049/jimmunol.1201574
57. Kanekiyo, M., Wei, C. J., Yassine, H. M., McTamney, P. M., Boyington, J. C., Whittle, J. R., et al. (2013). Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies. Nature 499, 102-106. doi: 10.1038/nature12202
58. Kees, U., and Krammer, P. H. (1984). Most influenza A virus-specific memory cytotoxic T lymphocytes react with antigenic epitopes associated with internal virus determinants. J. Exp. Med. 159, 365-377. doi: 10.1084/jem.159.2.365
59. Khurana, S., Loving, C. L., Manischewitz, J., King, L. R., Gauger, P. C., Henningson, J., et al. (2013). Vaccine-induced anti-HA2 antibodies promote virus fusion and enhance influenza virus respiratory disease. Sci. Transl. Med. 5:200ra114. doi: 10.1126/scitranslmed.3006366
60. Kjer-Nielsen, L., Patel, O., Corbett, A. J., Le Nours, J., Meehan, B., Liu, L., et al. (2012). MR1 presents microbial vitamin B metabolites to MAIT cells. Nature 491, 717-723. doi: 10.1038/nature11605
61. Kok, W. L., Denney, L., Benam, K., Cole, S., Clelland, C., McMichael, A. J., et al. (2012). Pivotal Advance: Invariant NKT cells reduce accumulation of inflammatory monocytes in the lungs and decrease immune-pathology during severe influenza A virus infection. J. Leukoc. Biol. 91, 357-368. doi: 10.1189/jlb.0411184
62. Krammer, F., Margine, I., Hai, R., Flood, A., Hirsh, A., Tsvetnitsky, V., et al. (2013). H3 stalk-based chimeric hemagglutinin influenza virus constructs protect mice from H7N9 challenge. J. Virol. 88, 2340-2343. doi: 10.1128/JVI.00641-13
63. Krammer, F., Pica, N., Hai, R., Tan, G. S., and Palese, P. (2012). Hemagglutinin stalk-reactive antibodies are boosted following sequential infection with seasonal and pandemic H1N1 Influenza virus in mice. J. Virol. 86, 10302-10307. doi: 10.1128/JVI.01336-12
64. Kreijtz, J. H., De Mutsert, G., Van Baalen, C. A., Fouchier, R. A., Osterhaus, A. D., and Rimmelzwaan, G. F. (2008). Cross-recognition of avian H5N1 influenza virus by human cytotoxic T lymphocyte populations directed to human influenza A virus. J. Virol. 82, 5161-5166 doi: 10.1128/JVI.02694-07
65. Lamere, M. W., Lam, H. T., Moquin, A., Haynes, L., Lund, F. E., Randall, T. D., et al. (2011). Contributions of antinucleoprotein IgG to heterosubtypic immunity against influenza virus. J. Immunol. 186, 4331-4339. doi: 10.4049/jimmunol.1003057
66. Lee, L. Y., Ha Do, L. A., Simmons, C., De Jong, M. D., Chau, N. V., Schumacher, R., et al. (2008). Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals. J. Clin. Invest. 118, 3478-3490. doi: 10.1172/JCI32460
67. Leeansyah, E., Ganesh, A., Quigley, M. F., Sonnerborg, A., Andersson, J., Hunt, P. W., et al. (2013). Activation, exhaustion, and persistent decline of the antimicrobial MR1-restricted MAIT-cell population in chronic HIV-1 infection. Blood 121, 1124-1135. doi: 10.1182/blood-2012-07-445429
68. Li, H., Xiang, Z., Feng, T., Li, J., Liu, Y., Fan, Y., et al. (2013). Human Vgamma9Vdelta2-T cells efficiently kill influenza virus-infected lung alveolar epithelial cells. Cell. Mol. Immunol. 10, 159-164. doi: 10.1038/cmi.2012.70
69. Lillie, P. J., Berthoud, T. K., Powell, T. J., Lambe, T., Mullarkey, C., Spencer, A. J., et al. (2012). Preliminary assessment of the efficacy of a T-cell-based influenza vaccine, MVA-NP+M1, in humans. Clin. Infect. Dis. 55, 19-25. doi: 10.1093/cid/cis327
70. Margine, I., Hai, R., Albrecht, R. A., Obermoser, G., Harrod, A. C., Banchereau, J., et al. (2013). H3N2 influenza virus infection induces broadly reactive hemagglutinin stalk antibodies in humans and mice. J. Virol. 87, 4728-4737. doi: 10.1128/JVI.03509-12
71. Marshall, D. R., Olivas, E., Andreansky, S., La Gruta, N. L., Neale, G. A., Gutierrez, A., et al. (2005). Effector CD8+ T cells recovered from an influenza pneumonia differentiate to a state of focused gene expression. Proc. Natl. Acad. Sci. U.S.A. 102, 6074-6079. doi: 10.1073/pnas.0501960102
72. McKinstry, K. K., Strutt, T. M., Kuang, Y., Brown, D. M., Sell, S., Dutton, R. W., et al. (2012). Memory CD4+ T cells protect against influenza through multiple synergizing mechanisms. J. Clin. Invest. 122, 2847-2856. doi: 10.1172/JCI63689
73. McMichael, A. J., Gotch, F. M., Dongworth, D. W., Clark, A., and Potter, C. W. (1983a). Declining T-cell immunity to influenza, 1977-82. Lancet 2, 762-764. doi: 10.1016/S0140-6736(83)92297-3
74. McMichael, A. J., Gotch, F. M., Noble, G. R., and Beare, P. A. (1983b). Cytotoxic T-cell immunity to influenza. N. Engl. J. Med. 309, 13-17. doi: 10.1056/NEJM198307073090103
75. Miller, J. D., Van Der Most, R. G., Akondy, R. S., Glidewell, J. T., Albott, S., Masopust, D., et al. (2008). Human effector and memory CD8+ T cell responses to smallpox and yellow fever vaccines. Immunity 28, 710-722. doi: 10.1016/j.immuni.2008.02.020
76. Monto, A. S., Ohmit, S. E., Petrie, J. G., Johnson, E., Truscon, R., Teich, E., et al. (2009). Comparative efficacy of inactivated and live attenuated influenza vaccines. N. Engl. J. Med. 361, 1260-1267. doi: 10.1056/NEJMoa0808652
77. Moore, C., John, M., James, I., Christiansen, F., Witt, C., and Mallal, S. (2002). Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level. Science 296, 1439-1443. doi: 10.1126/science.1069660
78. Mozdzanowska, K., Feng, J., Eid, M., Kragol, G., Cudic, M., Otvos, L., et al. (2003). Induction of influenza type A virus-specific resistance by immunization of mice with a synthetic multiple antigenic peptide vaccine that contains ectodomains of matrix protein 2. Vaccine 21, 2616-2626. doi: 10.1016/S0264-410X(03)00040-9
79. Neirynck, S., Deroo, T., Saelens, X., Vanlandschoot, P., Jou, W. M., and Fiers, W. (1999). A universal influenza A vaccine based on the extracellular domain of the M2 protein. Nat. Med. 5, 1157-1163. doi: 10.1038/13484
80. Okuno, Y., Isegawa, Y., Sasao, F., and Ueda, S. (1993). A common neutralizing epitope conserved between the hemagglutinins of influenza A virus H1 and H2 strains. J. Virol. 67, 2552-2558.
81. Oshansky, C. M., and Thomas, P. G. (2012). The human side of influenza. J. Leukoc. Biol. 92, 83-96. doi: 10.1189/jlb.1011506
82. Paget, C., Ivanov, S., Fontaine, J., Blanc, F., Pichavant, M., Renneson, J., et al. (2011). Potential role of invariant NKT cells in the control of pulmonary inflammation and CD8+ T cell response during acute influenza A virus H3N2 pneumonia. J. Immunol. 186, 5590-5602. doi: 10.4049/jimmunol.1002348
83. Paget, C., Ivanov, S., Fontaine, J., Renneson, J., Blanc, F., Pichavant, M., et al. (2012). Interleukin-22 is produced by invariant natural killer T lymphocytes during influenza A virus infection: potential role in protection against lung epithelial damages. J. Biol. Chem. 287, 8816-8829. doi: 10.1074/jbc.M111.304758
84. Pircher, H., Moskophidis, D., Rohrer, U., Burki, K., Hengartner, H., and Zinkernagel, R. (1990). Viral escape by selection of cytotoxic T cell-resistant virus variants in vivo. Nature 346, 629-633. doi: 10.1038/346629a0
85. Powell, T. J., Strutt, T., Reome, J., Hollenbaugh, J. A., Roberts, A. D., Woodland, D. L., et al. (2007). Priming with cold-adapted influenza A does not prevent infection but elicits long-lived protection against supralethal challenge with heterosubtypic virus. J. Immunol. 178, 1030-1038. doi: 10.4049/jimmunol.178.2.1030
86. Qin, G., Mao, H., Zheng, J., Sia, S. F., Liu, Y., Chan, P. L., et al. (2009). Phosphoantigen-expanded human gammadelta T cells display potent cytotoxicity against monocyte-derived macrophages infected with human and avian influenza viruses. J. Infect. Dis. 200, 858-865. doi: 10.1086/605413
87. Quinones-Parra, S., Grant, E., Loh, L., Nguyen, T. H., Campbell, K. A., Tong, S. Y., et al. (2014). Preexisting CD8+ T-cell immunity to the H7N9 influenza A virus varies across ethnicities. Proc. Natl. Acad. Sci. U.S.A. 111, 1049-1054. doi: 10.1073/pnas.1322229111
88. Rimmelzwaan, G. F., Berkhoff, E. G., Nieuwkoop, N. J., Smith, D. J., Fouchier, R. A., and Osterhaus, A. D. (2005). Full restoration of viral fitness by multiple compensatory co-mutations in the nucleoprotein of influenza A virus cytotoxic T-lymphocyte escape mutants. J. Gen. Virol. 86, 1801-1805. doi: 10.1099/vir.0.80867-0
89. Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., and Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nat. Rev. Immunol. 12, 845-857. doi: 10.1038/nri3328
90. Sant, A. J., and McMichael, A. (2012). Revealing the role of CD4(+) T cells in viral immunity. J. Exp. Med. 209, 1391-1395. doi: 10.1084/jem.20121517
91. Scherle, P. A., and Gerhard, W. (1986). Functional analysis of influenza-specific helper T cell clones in vivo. T cells specific for internal viral proteins provide cognate help for B cell responses to hemagglutinin. J. Exp. Med. 164, 1114-1128. doi: 10.1084/jem.164.4.1114
92. Sridhar, S., Begom, S., Bermingham, A., Hoschler, K., Adamson, W., Carman, W., et al. (2013). Cellular immune correlates of protection against symptomatic pandemic influenza. Nat. Med. 19, 1305-1312. doi: 10.1038/nm.3350
93. Steel, J., Lowen, A. C., Wang, T. T., Yondola, M., Gao, Q., Haye, K., et al. (2010). Influenza virus vaccine based on the conserved hemagglutinin stalk domain. MBio. 1, 1-9. doi: 10.1128/mBio.00018-10
94. Sukeno, N., Otsuki, Y., Konno, J., Yamane, N., Odagiri, T., Arikawa, J., et al. (1979). Anti-nucleoprotein antibody response in influenza A infection. Tohoku J. Exp. Med. 128, 241-249. doi: 10.1620/tjem.128.241
95. Sun, J. C., Williams, M. A., and Bevan, M. J. (2004). CD4+ T cells are required for the maintenance, not programming, of memory CD8+ T cells after acute infection. Nat. Immunol. 5, 927-933. doi: 10.1038/ni1105
96. Taylor, P. M., and Askonas, B. A. (1986). Influenza nucleoprotein-specific cytotoxic T-cell clones are protective in vivo. Immunology 58, 417-420.
97. Topham, D. J., and Doherty, P. C. (1998). Clearance of an influenza A virus by CD4+ T cells is inefficient in the absence of B cells. J. Virol. 72, 882-885.
98. Topham, D. J., Tripp, R. A., and Doherty, P. C. (1997). CD8+ T cells clear influenza virus by perforin or Fas-dependent processes. J. Immunol. 159, 5197-5200.
99. Topham, D. J., Tripp, R. A., Sarawar, S. R., Sangster, M. Y., and Doherty, P. C. (1996). Immune CD4+ T cells promote the clearance of influenza virus from major histocompatibility complex class II -/- respiratory epithelium. J. Virol. 70, 1288-1291.
100. Tu, W., Mao, H., Zheng, J., Liu, Y., Chiu, S. S., Qin, G., et al. (2010). Cytotoxic T lymphocytes established by seasonal human influenza cross-react against 2009 pandemic H1N1 influenza virus. J. Virol. 84, 6527-6535. doi: 10.1128/JVI.00519-10
101. Tu, W., Zheng, J., Liu, Y., Sia, S. F., Liu, M., Qin, G., et al. (2011). The aminobisphosphonate pamidronate controls influenza pathogenesis by expanding a gammadelta T cell population in humanized mice. J. Exp. Med. 208, 1511-1522. doi: 10.1084/jem.20110226
102. Ulmer, J. B., Donnelly, J. J., Parker, S. E., Rhodes, G. H., Felgner, P. L., Dwarki, V. J., et al. (1993). Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259, 1745-1749. doi: 10.1126/science.8456302
103. Ulmer, J. B., Fu, T. M., Deck, R. R., Friedman, A., Guan, L., Dewitt, C., et al. (1998). Protective CD4+ and CD8+ T cells against influenza virus induced by vaccination with nucleoprotein DNA. J. Virol. 72, 5648-5653.
104. Valkenburg, S. A., Quinones-Parra, S., Gras, S., Komadina, N., McVernon, J., Wang, Z., et al. (2013). Acute emergence and reversion of influenza A virus quasispecies within CD8(+) T cell antigenic peptides. Nat. Commun. 4:2663. doi: 10.1038/ncomms3663
105. Valkenburg, S. A., Venturi, V., Dang, T. H., Bird, N. L., Doherty, P. C., Turner, S. J., et al. (2012). Early priming minimizes the age-related immune compromise of CD8 T cell diversity and function. PLoS Pathog. 8:e1002544. doi: 10.1371/annotation/e142f9de-7f30-4759-bda1-a651e86d5ba6
106. Van De Sandt, C. E., Kreijtz, J. H., De Mutsert, G., Geelhoed-Mieras, M. M., Hillaire, M. L., Vogelzang-Van Trierum, S. E., et al. (2014). Human cytotoxic T lymphocytes directed to seasonal influenza A viruses cross-react with the newly emerging H7N9 virus. J. Virol. 88, 1684-1693. doi: 10.1128/JVI.02843-13
107. Vantourout, P., and Hayday, A. (2013). Six-of-the-best: unique contributions of gammadelta T cells to immunology. Nat. Rev. Immunol. 13, 88-100. doi: 10.1038/nri3384
108. Virelizier, J. L., Allison, A. C., Oxford, J. S., and Schild, G. C. (1977). Early presence of ribonucleoprotein antigen on surface of influenza virus-infected cells. Nature 266, 52-54. doi: 10.1038/266052a0
109. Voeten, J. T., Bestebroer, T. M., Nieuwkoop, N. J., Fouchier, R. A., Osterhaus, A. D., and Rimmelzwaan, G. F. (2000). Antigenic drift in the influenza A virus (H3N2) nucleoprotein and escape from recognition by cytotoxic T lymphocytes. J. Virol. 74, 6800-6807. doi: 10.1128/JVI.74.15.6800-6807.2000
110. Wahl, A., Schafer, F., Bardet, W., Buchli, R., Air, G. M., and Hildebrand, W. H. (2009). HLA class I molecules consistently present internal influenza epitopes. Proc. Natl. Acad. Sci. U.S.A. 106, 540-545. doi: 10.1073/pnas.0811271106
111. Wang, T. T., Tan, G. S., Hai, R., Pica, N., Ngai, L., Ekiert, D. C., et al. (2010). Vaccination with a synthetic peptide from the influenza virus hemagglutinin provides protection against distinct viral subtypes. Proc. Natl. Acad. Sci. U.S.A. 107, 18979-18984. doi: 10.1073/pnas.1013387107
112. Wei, C. J., Boyington, J. C., McTamney, P. M., Kong, W. P., Pearce, M. B., Xu, L., et al. (2010). Induction of broadly neutralizing H1N1 influenza antibodies by vaccination. Science 329, 1060-1064. doi: 10.1126/science.1192517
113. Whittle, J. R., Zhang, R., Khurana, S., King, L. R., Manischewitz, J., Golding, H., et al. (2011). Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin. Proc. Natl. Acad. Sci. U.S.A. 108, 14216-14221. doi: 10.1073/pnas.1111497108
114. Wilkinson, T. M., Li, C. K., Chui, C. S., Huang, A. K., Perkins, M., Liebner, J. C., et al. (2012). Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nat. Med. 18, 274-280. doi: 10.1038/nm.2612
115. Wu, C., Zanker, D., Valkenburg, S., Tan, B., Kedzierska, K., Zou, Q. M., et al. (2011). Systematic identification of immunodominant CD8+ T-cell responses to influenza A virus in HLA-A2 individuals. Proc. Natl. Acad. Sci. U.S.A. 108, 9178-9183. doi: 10.1073/pnas.1105624108
116. Wu, J. T., Ma, E. S., Lee, C. K., Chu, D. K., Ho, P. L., Shen, A. L., et al. (2010). The infection attack rate and severity of 2009 pandemic H1N1 influenza in Hong Kong. Clin. Infect. Dis. 51, 1184-1191. doi: 10.1086/656740
117. Yap, K. L., Ada, G. L., and McKenzie, I. F. (1978). Transfer of specific cytotoxic T lymphocytes protects mice inoculated with influenza virus. Nature 273, 238-239. doi: 10.1038/273238a0
118. Yewdell, J. W., Bennink, J. R., Smith, G. L., and Moss, B. (1985). Influenza A virus nucleoprotein is a major target antigen for cross-reactive anti-influenza A virus cytotoxic T lymphocytes. Proc. Natl. Acad. Sci. U.S.A. 82, 1785-1789. doi: 10.1073/pnas.82.6.1785
119. Yewdell, J. W., Frank, E., and Gerhard, W. (1981). Expression of influenza A virus internal antigens on the surface of infected P815 cells. J. Immunol. 126, 1814-1819.
120. Yoshida, R., Igarashi, M., Ozaki, H., Kishida, N., Tomabechi, D., Kida, H., et al. (2009). Cross-protective potential of a novel monoclonal antibody directed against antigenic site B of the hemagglutinin of influenza A viruses. PLoS Pathog. 5:e1000350. doi: 10.1371/journal.ppat.1000350
121. Zhao, Y., Zhang, Y. H., Denney, L., Young, D., Powell, T. J., Peng, Y. C., et al. (2012). High levels of virus-specific CD4+ T cells predict severe pandemic influenza A virus infection. Am. J. Respir. Crit. Care Med. 186, 1292-1297. doi: 10.1164/rccm.201207-1245OC