Harnessing the power of T cells: The promising hope for a universal influenza vaccine

Vaccines

Volumn 6, Issue 2, 2018, Pages

  Clemens, E Bridie ^a   Van de Sandt, Carolien ^a   Wong, Sook San ^b   Wakim, Linda M ^a   Valkenburg, Sophie A ^c  

^a UNIVERSITY OF MELBOURNE   (Australia)

^b ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

^c HKU PASTEUR RESEARCH CENTRE   (Hong Kong)

Author keywords

Influenza virus; T cell; Universal vaccine

Indexed keywords

EPITOPE; GAMMA INTERFERON; HLA ANTIGEN; INFLUENZA VACCINE; INTERLEUKIN 15; KRUPPEL LIKE FACTOR 2; MONOCLONAL ANTIBODY; T LYMPHOCYTE RECEPTOR; TRANSFORMING GROWTH FACTOR BETA;

CD8+ T LYMPHOCYTE; CLINICAL TRIAL (TOPIC); DISEASE SEVERITY; GENOTYPE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; IMMUNE RESPONSE; IMMUNOGENICITY; INFLUENZA A (H3N2); INFLUENZA A VIRUS (H1N1); INFLUENZA A VIRUS (H7N9); INNATE IMMUNITY; MAJOR HISTOCOMPATIBILITY COMPLEX; MEMORY T LYMPHOCYTE; NONHUMAN; PHENOTYPE; REGULATORY T LYMPHOCYTE; REVIEW; RISK FACTOR; T LYMPHOCYTE; VACCINATION; VIRUS LOAD;

EID: 85046466595     PISSN: None     EISSN: 2076393X     Source Type: Journal    
DOI: 10.3390/vaccines6020018     Document Type: Review

References (203)

1. Palache, A.; Abelin, A.; Hollingsworth, R.; Cracknell, W.; Jacobs, C.; Tsai, T.; Barbosa, P.; IFPMA Influenza Vaccine Supply (IFPMA IVS) task force. Survey of distribution of seasonal influenza vaccine doses in 201 countries (2004-2015): The 2003 World Health Assembly resolution on seasonal influenza vaccination coverage and the 2009 influenza pandemic have had very little impact on improving influenza control and pandemic preparedness. Vaccine 2017, 35, 4681-4686
2. Centers for Disease Control and Prevention; Appiah, G.D.; Blanton, L.; D’Mello, T.; Kniss, K.; Smith, S.; Mustaquim, D.; Steffens, C.; Dhara, R.; Cohen, J.; et al. Influenza activity—United States, 2014-15 season and composition of the 2015-16 influenza vaccine. MMWR 2015, 64, 583-590
3. Xie, H.; Wan, X.F.; Ye, Z.; Plant, E.P.; Zhao, Y.; Xu, Y.; Li, X.; Finch, C.; Zhao, N.; Kawano, T.; et al. H3N2 Mismatch of 2014-15 Northern Hemisphere Influenza Vaccines and Head-to-head Comparison between Human and Ferret Antisera derived Antigenic Maps. Sci. Rep. 2015, 5, 15279
4. Ambrose, C.S.; Levin, M.J. The rationale for quadrivalent influenza vaccines. Hum. Vaccines Immunother. 2012, 8, 81-88
5. Vijaykrishna, D.; Poon, L.L.; Zhu, H.C.; Ma, S.K.; Li, O.T.; Cheung, C.L.; Smith, G.J.; Peiris, J.S.; Guan, Y. Reassortment of pandemic H1N1/2009 influenza A virus in swine. Science 2010, 328, 1529
6. Wu, N.C.; Zost, S.J.; Thompson, A.J.; Oyen, D.; Nycholat, C.M.; McBride, R.; Paulson, J.C.; Hensley, S.E.; Wilson, I.A. A structural explanation for the low effectiveness of the seasonal influenza H3N2 vaccine. PLoS Pathog. 2017, 13, e1006682
7. Pebody, R.; McMenamin, J.; Nohynek, H. Live attenuated influenza vaccine (LAIV): Recent effectiveness results from the USA and implications for LAIV programmes elsewhere. Arch. Dis. Child. 2018, 103, 101-105
8. Caspard, H.; Gaglani, M.; Clipper, L.; Belongia, E.A.; McLean, H.Q.; Griffin, M.R.; Talbot, H.K.; Poehling, K.A.; Peters, T.R.; Veney, N.; et al. Effectiveness of live attenuated influenza vaccine and inactivated influenza vaccine in children 2-17 years of age in 2013-2014 in the United States. Vaccine 2016, 34, 77-82
9. Singanayagam, A.; Zambon, M.; Lalvani, A.; Barclay, W. Urgent challenges in implementing live attenuated influenza vaccine. Lancet Infect. Dis. 2018, 18, e25-e32
10. Belongia, E.A.; Kieke, B.A.; Donahue, J.G.; Greenlee, R.T.; Balish, A.; Foust, A.; Lindstrom, S.; Shay, D.K.; Marshfield Influenza Study Group. Effectiveness of inactivated influenza vaccines varied substantially with antigenic match from the 2004-2005 season to the 2006-2007 season. J. Infect. Dis. 2009, 199, 159-167
11. Wong, S.S.; Kaplan, B.; Zanin, M.; Debeauchamp, J.; Kercher, L.; Crumpton, J.C.; Seiler, P.; Sun, Y.; Tang, L.; Krauss, S.; et al. Impact of Adjuvants on the Immunogenicity and Efficacy of Split-Virion H7N9 Vaccine in Ferrets. J. Infect. Dis.2015, 212, 542-551
12. Liu, R.; Moise, L.; Tassone, R.; Gutierrez, A.H.; Terry, F.E.; Sangare, K.; Ardito, M.T.; Martin, W.D.; De Groot, A.S. H7N9 T-cell epitopes that mimic human sequences are less immunogenic and may induce Treg-mediated tolerance. Hum. Vaccines Immunother. 2015, 11, 2241-2252
13. Rockman, S.; Brown, L. Pre-pandemic and pandemic influenza vaccines. Hum. Vaccines 2010, 6, 792-801
14. Bodewes, R.; Kreijtz, J.H.; Baas, C.; Geelhoed-Mieras, M.M.; de Mutsert, G.; van Amerongen, G.; van den Brand, J.M.; Fouchier, R.A.; Osterhaus, A.D.; Rimmelzwaan, G.F. Vaccination against human influenza A/H3N2 virus prevents the induction of heterosubtypic immunity against lethal infection with avian influenza A/H5N1 virus. PLoS ONE 2009, 4, e5538
15. Croft, N.P.; Purcell, A.W.; Tscharke, D.C. Quantifying epitope presentation using mass spectrometry. Mol. Immunol. 2015, 68, 77-80
16. Assarsson, E.; Bui, H.H.; Sidney, J.; Zhang, Q.; Glenn, J.; Oseroff, C.; Mbawuike, I.N.; Alexander, J.; Newman, M.J.; Grey, H.; et al. Immunomic analysis of the repertoire of T-cell specificities for influenza A virus in humans. J. Virol. 2008, 82, 12241-12251
17. Lee, L.Y.; Ha do, L.A.; Simmons, C.; de Jong, M.D.; Chau, N.V.; Schumacher, R.; Peng, Y.C.; McMichael, A.J.; Farrar, J.J.; Smith, G.L.; et al. Memory T cells established by seasonal human influenza A infection cross-react with avian influenza A (H5N1) in healthy individuals. J. Clin. Investig. 2008, 118, 3478-3490
18. + T-cell immunity to the H7N9 influenza A virus varies across ethnicities. Proc. Natl. Acad. Sci. USA 2014, 111, 1049-1054
19. Van de Sandt, C.E.; Kreijtz, J.H.; de Mutsert, G.; Geelhoed-Mieras, M.M.; Hillaire, M.L.; Vogelzang-van Trierum, S.E.; Osterhaus, A.D.; Fouchier, R.A.; Rimmelzwaan, G.F. Human cytotoxic T lymphocytes directed to seasonal influenza A viruses cross-react with the newly emerging H7N9 virus. J. Virol. 2014, 88, 1684-1693
20. Kreijtz, J.H.; de Mutsert, G.; van Baalen, C.A.; Fouchier, R.A.; Osterhaus, A.D.; Rimmelzwaan, G.F. Cross-recognition of avian H5N1 influenza virus by human cytotoxic T-lymphocyte populations directed to human influenza A virus. J. Virol.2008, 82, 5161-5166
21. Hillaire, M.L.; Vogelzang-van Trierum, S.E.; Kreijtz, J.H.; de Mutsert, G.; Fouchier, R.A.; Osterhaus, A.D.; Rimmelzwaan, G.F. 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. 2013, 94, 583-592
22. Hillaire, M.L.; van Trierum, S.E.; Kreijtz, J.H.; Bodewes, R.; Geelhoed-Mieras, M.M.; Nieuwkoop, N.J.; Fouchier, R.A.; Kuiken, T.; Osterhaus, A.D.; Rimmelzwaan, G.F. Cross-protective immunity against influenza pH1N1 2009 viruses induced by seasonal influenza A (H3N2) virus is mediated by virus-specific T-cells. J. Gen. Virol.2011, 92, 2339-2349
23. Kreijtz, J.H.; Bodewes, R.; van Amerongen, G.; Kuiken, T.; Fouchier, R.A.; Osterhaus, A.D.; Rimmelzwaan, G.F. Primary influenza A virus infection induces cross-protective immunity against a lethal infection with a heterosubtypic virus strain in mice. Vaccine 2007, 25, 612-620
24. Kreijtz, J.H.; Bodewes, R.; van den Brand, J.M.; de Mutsert, G.; Baas, C.; van Amerongen, G.; Fouchier, R.A.; Osterhaus, A.D.; Rimmelzwaan, G.F. Infection of mice with a human influenza A/H3N2 virus induces protective immunity against lethal infection with influenza A/H5N1 virus. Vaccine 2009, 27, 4983-4989
25. Bodewes, R.; Kreijtz, J.H.; Geelhoed-Mieras, M.M.; van Amerongen, G.; Verburgh, R.J.; van Trierum, S.E.; Kuiken, T.; Fouchier, R.A.; Osterhaus, A.D.; Rimmelzwaan, G.F. Vaccination against seasonal influenza A/H3N2 virus reduces the induction of heterosubtypic immunity against influenza A/H5N1 virus infection in ferrets. J. Virol.2011, 85, 2695-2702
26. Christensen, J.P.; Doherty, P.C.; Branum, K.C.; Riberdy, J.M. Profound protection against respiratory challenge with a lethal H7N7 influenza A virus by increasing the magnitude of CD8(+) T-cell memory. J. Virol. 2000, 74, 11690-11696
27. Thyagarajan, B.; Bloom, J.D. The inherent mutational tolerance and antigenic evolvability of influenza hemagglutinin. Elife 2014, 3, e03300
28. + T-Cell Epitopes of Influenza Virus Nucleoprotein Revealed by a Comparative Analysis of Human and Swine Viral Lineages. J. Virol. 2015, 89, 11275-11283
29. + T cells for heterosubtypic protection. Proc. Natl. Acad. Sci. USA 2014, 111, 5676-5681
30. Wang, Z.; Wan, Y.; Qiu, C.; Quinones-Parra, S.; Zhu, Z.; Loh, L.; Tian, D.; Ren, Y.; Hu, Y.; Zhang, X.; et al. Recovery from severe H7N9 disease is associated with diverse response mechanisms dominated by CD8(+) T cells. Nat. Commun. 2015, 6, 6833
31. Terajima, M.; Babon, J.A.; Co, M.D.; Ennis, F.A. Cross-reactive human B cell and T cell epitopes between influenza A and B viruses. Virol. J. 2013, 10, 244
32. Koutsakos, M.; Nguyen, T.H.; Barclay, W.S.; Kedzierska, K. Knowns and unknowns of influenza B viruses. Future Microbiol. 2016, 11, 119-135
33. Sun, J.C.; Bevan, M.J. Defective CD8 T cell memory following acute infection without CD4 T cell help. Science 2003, 300, 339-342
34. Crotty, S. A brief history of T cell help to B cells. Nat. Rev. Immunol. 2015, 15, 185-189
35. DiPiazza, A.; Nogales, A.; Poulton, N.; Wilson, P.C.; Martinez-Sobrido, L.; Sant, A.J. Pandemic 2009 H1N1 Influenza Venus reporter virus reveals broad diversity of MHC class II-positive antigen-bearing cells following infection in vivo. Sci. Rep. 2017, 7, 10857
36. Arstila, T.P.; Casrouge, A.; Baron, V.; Even, J.; Kanellopoulos, J.; Kourilsky, P. A direct estimate of the human alphabeta T cell receptor diversity. Science 1999, 286, 958-961
37. Trautmann, L.; Rimbert, M.; Echasserieau, K.; Saulquin, X.; Neveu, B.; Dechanet, J.; Cerundolo, V.; Bonneville, M. Selection of T cell clones expressing high-affinity public TCRs within Human cytomegalovirus-specific CD8 T cell responses. J. Immunol.2005, 175, 6123-6132
38. La Gruta, N.L.; Rothwell, W.T.; Cukalac, T.; Swan, N.G.; Valkenburg, S.A.; Kedzierska, K.; Thomas, P.G.; Doherty, P.C.; Turner, S.J. Primary CTL response magnitude in mice is determined by the extent of naive T cell recruitment and subsequent clonal expansion. J. Clin. Investig. 2010, 120, 1885-1894
39. Kim, S.K.; Brehm, M.A.; Welsh, R.M.; Selin, L.K. Dynamics of memory T cell proliferation under conditions of heterologous immunity and bystander stimulation. J. Immunol. 2002, 169, 90-98
40. Wedemeyer, H.; Mizukoshi, E.; Davis, A.R.; Bennink, J.R.; Rehermann, B. Cross-reactivity between hepatitis C virus and Influenza A virus determinant-specific cytotoxic T cells. J. Virol. 2001, 75, 11392-11400
41. + T cells from patients with cervical cancer are cross-reactive with the coronavirus NS2 protein. J. Virol. 2003, 77, 5464-5474
42. + T cells contribute to lymphoproliferation in Epstein-Barr virus-associated infectious mononucleosis. J. Clin. Investig. 2005, 115, 3602-3612
43. Clute, S.C.; Naumov, Y.N.; Watkin, L.B.; Aslan, N.; Sullivan, J.L.; Thorley-Lawson, D.A.; Luzuriaga, K.; Welsh, R.M.; Puzone, R.; Celada, F.; et al. Broad cross-reactive TCR repertoires recognizing dissimilar Epstein-Barr and influenza A virus epitopes. J. Immunol. 2010, 185, 6753-6764
44. Spaulding, A.C.; Kurane, I.; Ennis, F.A.; Rothman, A.L. Analysis of murine CD8(+) T-cell clones specific for the Dengue virus NS3 protein: Flavivirus cross-reactivity and influence of infecting serotype. J. Virol. 1999, 73, 398-403
45. + T-cell immunity against influenza viruses. Proc. Natl. Acad. Sci. USA 2016, 113, 4440-4445
46. Cukalac, T.; Chadderton, J.; Zeng, W.; Cullen, J.G.; Kan, W.T.; Doherty, P.C.; Jackson, D.C.; Turner, S.J.; La Gruta, N.L. The influenza virus-specific CTL immunodominance hierarchy in mice is determined by the relative frequency of high-avidity T cells. J. Immunol. 2014, 192, 4061-4068
47. Tscharke, D.C.; Croft, N.P.; Doherty, P.C.; La Gruta, N.L. Sizing up the key determinants of the CD8(+) T cell response. Nat. Rev. Immunol. 2015, 15, 705-716
48. Deliyannis, G.; Jackson, D.C.; Ede, N.J.; Zeng, W.; Hourdakis, I.; Sakabetis, E.; Brown, L.E. Induction of long-term memory CD8(+) T cells for recall of viral clearing responses against influenza virus. J. Virol. 2002, 76, 4212-4221
49. + T cells correlate with disease protection against influenza challenge in humans. Nat. Med. 2012, 18, 274-280
50. Wagar, L.E.; Rosella, L.; Crowcroft, N.; Lowcock, B.; Drohomyrecky, P.C.; Foisy, J.; Gubbay, J.; Rebbapragada, A.; Winter, A.L.; Achonu, C.; et al. Humoral and cell-mediated immunity to pandemic H1N1 influenza in a Canadian cohort one year post-pandemic: Implications for vaccination. PLoS ONE 2011, 6, e28063
51. Hammarlund, E.; Lewis, M.W.; Hansen, S.G.; Strelow, L.I.; Nelson, J.A.; Sexton, G.J.; Hanifin, J.M.; Slifka, M.K. Duration of antiviral immunity after smallpox vaccination. Nat. Med. 2003, 9, 1131-1137
52. + T cell response is long-lived. J. Infect. Dis. 2015, 212, 81-85
53. Powell, T.J.; Strutt, T.; Reome, J.; Hollenbaugh, J.A.; Roberts, A.D.; Woodland, D.L.; Swain, S.L.; Dutton, R.W. Priming with cold-adapted influenza A does not prevent infection but elicits long-lived protection against supralethal challenge with heterosubtypic virus. J. Immunol. 2007, 178, 1030-1038
54. Li, J.; Arevalo, M.T.; Chen, Y.; Chen, S.; Zeng, M. T-cell-mediated cross-strain protective immunity elicited by prime-boost vaccination with a live attenuated influenza Vaccine. Int. J. Infect. Dis. 2014, 27, 37-43
55. Slutter, B.; Pewe, L.L.; Lauer, P.; Harty, J.T. Cutting edge: Rapid boosting of cross-reactive memory CD8 T cells broadens the protective capacity of the Flumist Vaccine. J. Immunol. 2013, 190, 3854-3858
56. Ashkenazi, S.; Vertruyen, A.; Aristegui, J.; Esposito, S.; McKeith, D.D.; Klemola, T.; Biolek, J.; Kuhr, J.; Bujnowski, T.; Desgrandchamps, D.; et al. Superior relative efficacy of live attenuated influenza Vaccine compared with inactivated influenza Vaccine in young children with recurrent respiratory tract infections. Pediatr. Infect. Dis. J. 2006, 25, 870-879
57. Belshe, R.B.; Edwards, K.M.; Vesikari, T.; Black, S.V.; Walker, R.E.; Hultquist, M.; Kemble, G.; Connor, E.M.; Group C-TCES. Live attenuated versus inactivated influenza Vaccine in infants and young children. N. Engl. J. Med. 2007, 356, 685-696
58. Cox, R.J.; Brokstad, K.A.; Ogra, P. Influenza virus: Immunity and vaccination strategies. Comparison of the immune response to inactivated and live, attenuated influenza Vaccines. Scand. J. Immunol. 2004, 59, 1-15
59. Hoft, D.F.; Babusis, E.; Worku, S.; Spencer, C.T.; Lottenbach, K.; Truscott, S.M.; Abate, G.; Sakala, I.G.; Edwards, K.M.; Creech, C.B.; et al. Live and inactivated influenza Vaccines induce similar humoral responses, but only live Vaccines induce diverse T-cell responses in young children. J. Infect. Dis. 2011, 204, 845-853
60. Mohn, K.G.I.; Zhou, F.; Brokstad, K.A.; Sridhar, S.; Cox, R.J. Boosting of Cross-Reactive and Protection-Associated T Cells in Children After Live Attenuated Influenza Vaccination. J. Infect. Dis. 2017, 215, 1527-1535
61. He, Q.; Martinez-Sobrido, L.; Eko, F.O.; Palese, P.; Garcia-Sastre, A.; Lyn, D.; Okenu, D.; Bandea, C.; Ananaba, G.A.; Black, C.M.; et al. Live-attenuated influenza viruses as delivery vectors for Chlamydia Vaccines. Immunology 2007, 122, 28-37
62. Sridhar, S.; Begom, S.; Bermingham, A.; Ziegler, T.; Roberts, K.L.; Barclay, W.S.; Openshaw, P.; Lalvani, A. Predominance of heterosubtypic IFN-gamma-only-secreting effector memory T cells in pandemic H1N1 naive adults. Eur. J. Immunol.2012, 42, 2913-2924
63. He, X.S.; Holmes, T.H.; Zhang, C.; Mahmood, K.; Kemble, G.W.; Lewis, D.B.; Dekker, C.L.; Greenberg, H.B.; Arvin, A.M. Cellular immune responses in children and adults receiving inactivated or live attenuated influenza Vaccines. J. Virol. 2006, 80, 11756-11766
64. Mbawuike, I.N.; Piedra, P.A.; Cate, T.R.; Couch, R.B. Cytotoxic T lymphocyte responses of infants after natural infection or immunization with live cold-recombinant or inactivated influenza A virus Vaccine. J. Med. Virol. 1996, 50, 105-111
65. Bonduelle, O.; Yahia, N.; Siberil, S.; Benhabiles, N.; Carrat, F.; Krivine, A.; Rozenberg, F.; Dimitrov, J.; Kaveri, S.V.; Curjol, A.; et al. Longitudinal and integrative biomodeling of effector and memory immune compartments after inactivated influenza vaccination. J. Immunol. 2013, 191, 623-631
66. Basha, S.; Hazenfeld, S.; Brady, R.C.; Subbramanian, R.A. Comparison of antibody and T-cell responses elicited by licensed inactivated-and live-attenuated influenza Vaccines against H3N2 hemagglutinin. Hum. Immunol. 2011, 72, 463-469
67. Mohn, K.G.; Bredholt, G.; Brokstad, K.A.; Pathirana, R.D.; Aarstad, H.J.; Tondel, C.; Cox, R.J. Longevity of B-cell and T-cell responses after live attenuated influenza vaccination in children. J. Infect. Dis. 2015, 211, 1541-1549
68. Wohlgemuth, N.; Ye, Y.; Fenstermacher, K.J.; Liu, H.; Lane, A.P.; Pekosz, A. The M2 protein of live, attenuated influenza Vaccine encodes a mutation that reduces replication in human nasal epithelial cells. Vaccine 2017, 35, 6691-6699
69. Gao, W.; Soloff, A.C.; Lu, X.; Montecalvo, A.; Nguyen, D.C.; Matsuoka, Y.; Robbins, P.D.; Swayne, D.E.; Donis, R.O.; Katz, J.M.; et al. Protection of mice and poultry from lethal H5N1 avian influenza virus through adenovirus-based immunization. J. Virol.2006, 80, 1959-1964
70. + T-cell immunogenicity in humans of a novel heterosubtypic influenza A Vaccine, MVA-NP+M1. Clin. Infect. Dis. 2011, 52, 1-7
71. Mifsud, E.J.; Tan, A.C.; Short, K.R.; Brown, L.E.; Chua, B.Y.; Jackson, D.C. Reducing the impact of influenza-associated secondary pneumococcal infections. Immunol. Cell Biol. 2016, 94, 101-108
72. + T Cells. J. Virol. 2016, 90, 6976-6988
73. Fan, R.L.; Valkenburg, S.A.; Wong, C.K.; Li, O.T.; Nicholls, J.M.; Rabadan, R.; Peiris, J.S.; Poon, L.L. Generation of Live Attenuated Influenza Virus by Using Codon Usage Bias. J. Virol. 2015, 89, 10762-10773
74. Steel, J.; Lowen, A.C.; Pena, L.; Angel, M.; Solorzano, A.; Albrecht, R.; Perez, D.R.; Garcia-Sastre, A.; Palese, P. Live attenuated influenza viruses containing NS1 truncations as Vaccine candidates against H5N1 highly pathogenic avian influenza. J. Virol. 2009, 83, 1742-1753
75. Baz, M.; Boonnak, K.; Paskel, M.; Santos, C.; Powell, T.; Townsend, A.; Subbarao, K. Nonreplicating influenza A virus Vaccines confer broad protection against lethal challenge. MBio 2015, 6, e01487-15
76. + T cells, non-neutralizing antibodies, and alveolar macrophages is important for heterosubtypic influenza virus immunity. PLoS Pathog. 2013, 9, e1003207
77. Forrest, B.D.; Pride, M.W.; Dunning, A.J.; Capeding, M.R.; Chotpitayasunondh, T.; Tam, J.S.; Rappaport, R.; Eldridge, J.H.; Gruber, W.C. Correlation of cellular immune responses with protection against culture-confirmed influenza virus in young children. Clin. Vaccine Immunol. 2008, 15, 1042-1053
78. Loh, L.; Wang, Z.; Sant, S.; Koutsakos, M.; Jegaskanda, S.; Corbett, A.J.; Liu, L.; Fairlie, D.P.; Crowe, J.; Rossjohn, J.; et al. Human mucosal-associated invariant T cells contribute to antiviral influenza immunity via IL-18-dependent activation. Proc. Natl. Acad. Sci. USA 2016, 113, 10133-10138
79. Spitaels, J.; Roose, K.; Saelens, X. Influenza and Memory T Cells: How to Awake the Force. Vaccines 2016, 4, 33
80. DiPiazza, A.; Richards, K.A.; Knowlden, Z.A.; Nayak, J.L.; Sant, A.J. The Role of CD4 T Cell Memory in Generating Protective Immunity to Novel and Potentially Pandemic Strains of Influenza. Front. Immunol. 2016, 7, 10
81. Riberdy, J.M.; Christensen, J.P.; Branum, K.; Doherty, P.C. Diminished primary and secondary influenza virus-specific CD8(+) T-cell responses in CD4-depleted Ig(-/-) mice. J. Virol. 2000, 74, 9762-9765
82. Belz, G.T.; Wodarz, D.; Diaz, G.; Nowak, M.A.; Doherty, P.C. Compromised influenza virus-specific CD8(+)-T-cell memory in CD4(+)-T-cell-deficient mice. J. Virol. 2002, 76, 12388-12393
83. Corti, D.; Lanzavecchia, A. Broadly neutralizing antiviral antibodies. Annu. Rev. Immunol. 2013, 31, 705-742
84. Koutsakos, M.; Wheatley, A.K.; Loh, L.; Clemens, E.B.; Sant, S.; Nussing, S.; Fox, A.; Chung, A.W.; Laurie, K.L.; Hurt, A.C.; et al. Circulating TFH cells, serological memory, and tissue compartmentalization shape human influenza-specific B cell immunity. Sci. Transl. Med. 2018, 10
85. Alam, S.; Chan, C.; Qiu, X.; Shannon, I.; White, C.L.; Sant, A.J.; Nayak, J.L. Selective pre-priming of HA-specific CD4 T cells restores immunological reactivity to HA on heterosubtypic influenza infection. PLoS ONE 2017, 12, e0176407
86. Richards, K.A.; Nayak, J.; Chaves, F.A.; DiPiazza, A.; Knowlden, Z.A.; Alam, S.; Treanor, J.J.; Sant, A.J. Seasonal Influenza Can Poise Hosts for CD4 T-Cell Immunity to H7N9 Avian Influenza. J. Infect. Dis. 2015, 212, 86-94
87. + T-cell responses. J. Infect. Dis. 2015, 211, 1408-1417
88. Gostic, K.M.; Ambrose, M.; Worobey, M.; Lloyd-Smith, J.O. Potent protection against H5N1 and H7N9 influenza via childhood hemagglutinin imprinting. Science 2016, 354, 722-726
89. Brown, D.M.; Dilzer, A.M.; Meents, D.L.; Swain, S.L. CD4 T cell-mediated protection from lethal influenza: Perforin and antibody-mediated mechanisms give a one-two punch. J. Immunol. 2006, 177, 2888-2898
90. Cowling, B.J.; Chan, K.H.; Fang, V.J.; Lau, L.L.H.; So, H.C.; Fung, R.O.P.; Ma, E.S.K.; Kwong, A.S.K.; Chan, C.W.; Tsui, W.W.S.; et al. Comparative epidemiology of pandemic and seasonal influenza A in households. N. Engl. J. Med. 2010, 362, 2175-2184
91. Epstein, S.L. Prior H1N1 influenza infection and susceptibility of Cleveland Family Study participants during the H2N2 pandemic of 1957: An experiment of nature. J. Infect. Dis. 2006, 193, 49-53
92. Slepushkin, A.N. The effect of a previous attack of A1 influenza on susceptibility to A2 virus during the 1957 outbreak. Bull. World Health Organ. 1959, 20, 297-301
93. Oshansky, C.M.; Gartland, A.J.; Wong, S.S.; Jeevan, T.; Wang, D.; Roddam, P.L.; Caniza, M.A.; Hertz, T.; Devincenzo, J.P.; Webby, R.J.; et al. Mucosal immune responses predict clinical outcomes during influenza infection independently of age and viral load. Am. J. Respir. Crit. Care Med. 2014, 189, 449-462
94. Sridhar, S.; Begom, S.; Bermingham, A.; Hoschler, K.; Adamson, W.; Carman, W.; Bean, T.; Barclay, W.; Deeks, J.J.; Lalvani, A. Cellular immune correlates of protection against symptomatic pandemic influenza. Nat. Med. 2013, 19, 1305-1312
95. Hayward, A.C.; Wang, L.; Goonetilleke, N.; Fragaszy, E.B.; Bermingham, A.; Copas, A.; Dukes, O.; Millett, E.R.; Nazareth, I.; Nguyen-Van-Tam, J.S.; et al. Natural T Cell-mediated Protection against Seasonal and Pandemic Influenza. Results of the Flu Watch Cohort Study. Am. J. Respir. Crit. Care Med. 2015, 191, 1422-1431
96. Fox, A.; Le, N.M.; Horby, P.; van Doorn, H.R.; Nguyen, V.T.; Nguyen, H.H.; Nguyen, T.C.; Vu, D.P.; Nguyen, M.H.; Diep, N.T.; et al. Severe pandemic H1N1 2009 infection is associated with transient NK and T deficiency and aberrant CD8 responses. PLoS ONE 2012, 7, e31535
97. Wong, S.S.; Oshansky, C.M.; Guo, X.J.; Ralston, J.; Wood, T.; Reynolds, G.; Seeds, R.; Newbern, C.; Waite, B.; Widdowson, M.A.; et al. Severe influenza is characterized by prolonged immune activation: Results from the SHIVERS cohort study. J. Infect. Dis.2017, 217, 245-256
98. + T cells predict severe pandemic influenza A virus infection. Am. J. Respir. Crit. Care Med. 2012, 186, 1292-1297
99. McMichael, A.J.; Gotch, F.M.; Noble, G.R.; Beare, P.A. Cytotoxic T-cell immunity to influenza. N. Engl. J. Med. 1983, 309, 13-17
100. + cells. PLoS ONE 2014, 9, e92823
101. Davey, R.T., Jr.; Lynfield, R.; Dwyer, D.E.; Losso, M.H.; Cozzi-Lepri, A.; Wentworth, D.; Lane, H.C.; Dewar, R.; Rupert, A.; Metcalf, J.A.; et al. The association between serum biomarkers and disease outcome in influenza A(H1N1)pdm09 virus infection: Results of two international observational cohort studies. PLoS ONE 2013, 8, e57121
102. Fiore-Gartland, A.; Panoskaltsis-Mortari, A.; Agan, A.A.; Mistry, A.J.; Thomas, P.G.; Matthay, M.A.; Investigators, P.P.; Hertz, T.; Randolph, A.G. Cytokine Profiles of Severe Influenza Virus-Related Complications in Children. Front. Immunol. 2017, 8, 1423
103. Slutter, B.; Pewe, L.L.; Kaech, S.M.; Harty, J.T. Lung airway-surveilling CXCR3(hi) memory CD8(+) T cells are critical for protection against influenza A virus. Immunity 2013, 39, 939-948
104. Duan, S.; Thomas, P.G. Balancing Immune Protection and Immune Pathology by CD8(+) T-Cell Responses to Influenza Infection. Front. Immunol. 2016, 7, 25
105. + T Cells Damage Noninfected Epithelial Cells during Influenza Virus Infection In Vitro. Am. J. Respir. Cell Mol. Biol. 2017, 57, 536-546
106. Mohn, K.G.; Cox, R.J.; Tunheim, G.; Berdal, J.E.; Hauge, A.G.; Jul-Larsen, A.; Norwegian Pandemic, G.; Peters, B.; Oftung, F.; Jonassen, C.M.; et al. Immune Responses in Acute and Convalescent Patients with Mild, Moderate and Severe Disease during the 2009 Influenza Pandemic in Norway. PLoS ONE 2015, 10, e0143281
107. Lee, N.; Chan, P.K.; Wong, C.K.; Wong, K.T.; Choi, K.W.; Joynt, G.M.; Lam, P.; Chan, M.C.; Wong, B.C.; Lui, G.C.; et al. Viral clearance and inflammatory response patterns in adults hospitalized for pandemic 2009 influenza A(H1N1) virus pneumonia. Antivir. Ther. 2011, 16, 237-247
108. Yang, Z.F.; Mok, C.K.; Liu, X.Q.; Li, X.B.; He, J.F.; Guan, W.D.; Xu, Y.H.; Pan, W.Q.; Chen, L.Y.; Lin, Y.P.; et al. Clinical, virological and immunological features from patients infected with re-emergent avian-origin human H7N9 influenza disease of varying severity in Guangdong province. PLoS ONE 2015, 10, e0117846
109. Wang, Z.; Zhang, A.; Wan, Y.; Liu, X.; Qiu, C.; Xi, X.; Ren, Y.; Wang, J.; Dong, Y.; Bao, M.; et al. Early hypercytokinemia is associated with interferon-induced transmembrane protein-3 dysfunction and predictive of fatal H7N9 infection. Proc. Natl. Acad. Sci. USA 2014, 111, 769-774
110. + memory T cell responses directed against common respiratory pathogens in peripheral blood and lung. J. Infect. Dis. 2007, 195, 1718-1725
111. Wong, S.S.; Duan, S.; DeBeauchamp, J.; Zanin, M.; Kercher, L.; Sonnberg, S.; Fabrizio, T.; Jeevan, T.; Crumpton, J.C.; Oshansky, C.; et al. The immune correlates of protection for an avian influenza H5N1 Vaccine in the ferret model using oil-in-water adjuvants. Sci. Rep. 2017, 7, 44727
112. Schenkel, J.M.; Masopust, D. Tissue-resident memory T cells. Immunity 2014, 41, 886-897
113. + T cells specific for respiratory viruses in the human lung. J. Exp. Med. 2005, 202, 1433-1442
114. Purwar, R.; Campbell, J.; Murphy, G.; Richards, W.G.; Clark, R.A.; Kupper, T.S. Resident memory T cells (T(RM)) are abundant in human lung: Diversity, function, and antigen specificity. PLoS ONE 2011, 6, e16245
115. Steinert, E.M.; Schenkel, J.M.; Fraser, K.A.; Beura, L.K.; Manlove, L.S.; Igyarto, B.Z.; Southern, P.J.; Masopust, D. Quantifying Memory CD8 T Cells Reveals Regionalization of Immunosurveillance. Cell 2015, 161, 737-749
116. Mueller, S.N.; Mackay, L.K. Tissue-resident memory T cells: Local specialists in immune defence. Nat. Rev. Immunol. 2016, 16, 79-89
117. Gebhardt, T.; Wakim, L.M.; Eidsmo, L.; Reading, P.C.; Heath, W.R.; Carbone, F.R. Memory T cells in nonlymphoid tissue that provide enhanced local immunity during infection with herpes simplex virus. Nat. Immunol. 2009, 10, 524-530
118. Mackay, L.K.; Stock, A.T.; Ma, J.Z.; Jones, C.M.; Kent, S.J.; Mueller, S.N.; Heath, W.R.; Carbone, F.R.; Gebhardt, T. Long-lived epithelial immunity by tissue-resident memory T (TRM) cells in the absence of persisting local antigen presentation. Proc. Natl. Acad. Sci. USA 2012, 109, 7037-7042
119. Ariotti, S.; Hogenbirk, M.A.; Dijkgraaf, F.E.; Visser, L.L.; Hoekstra, M.E.; Song, J.Y.; Jacobs, H.; Haanen, J.B.; Schumacher, T.N. T cell memory. Skin-resident memory CD8(+) T cells trigger a state of tissue-wide pathogen alert. Science 2014, 346, 101-105
120. Schenkel, J.M.; Fraser, K.A.; Vezys, V.; Masopust, D. Sensing and alarm function of resident memory CD8(+) T cells. Nat. Immunol. 2013, 14, 509-513
121. Teijaro, J.R.; Turner, D.; Pham, Q.; Wherry, E.J.; Lefrancois, L.; Farber, D.L. Cutting edge: Tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection. J. Immunol. 2011, 187, 5510-5514
122. Turner, D.L.; Bickham, K.L.; Thome, J.J.; Kim, C.Y.; D’Ovidio, F.; Wherry, E.J.; Farber, D.L. Lung niches for the generation and maintenance of tissue-resident memory T cells. Mucosal Immunol. 2013, 7, 501
123. Hombrink, P.; Helbig, C.; Backer, R.A.; Piet, B.; Oja, A.E.; Stark, R.; Brasser, G.; Jongejan, A.; Jonkers, R.E.; Nota, B.; et al. Programs for the persistence, vigilance and control of human CD8(+) lung-resident memory T cells. Nat. Immunol. 2016, 17, 1467-1478
124. Wu, T.; Hu, Y.; Lee, Y.T.; Bouchard, K.R.; Benechet, A.; Khanna, K.; Cauley, L.S. Lung-resident memory CD8 T cells (TRM) are indispensable for optimal cross-protection against pulmonary virus infection. J. Leukoc. Biol. 2014, 95, 215-224
125. Lee, Y.T.; Suarez-Ramirez, J.E.; Wu, T.; Redman, J.M.; Bouchard, K.; Hadley, G.A.; Cauley, L.S. Environmental and antigen receptor-derived signals support sustained surveillance of the lungs by pathogen-specific cytotoxic T lymphocytes. J. Virol. 2011, 85, 4085-4094
126. Piet, B.; de Bree, G.J.; Smids-Dierdorp, B.S.; van der Loos, C.M.; Remmerswaal, E.B.; von der Thusen, J.H.; van Haarst, J.M.; Eerenberg, J.P.; ten Brinke, A.; van der Bij, W.; et al. CD8(+) T cells with an intraepithelial phenotype upregulate cytotoxic function upon influenza infection in human lung. J. Clin. Investig. 2011, 121, 2254-2263
127. Sathaliyawala, T.; Kubota, M.; Yudanin, N.; Turner, D.; Camp, P.; Thome, J.J.; Bickham, K.L.; Lerner, H.; Goldstein, M.; Sykes, M.; et al. Distribution and compartmentalization of human circulating and tissue-resident memory T cell subsets. Immunity 2013, 38, 187-197
128. Pizzolla, A.; Nguyen, T.H.; Sant, S.; Jaffar, J.; Loudovaris, T.; Mannering, S.I.; Thomas, P.G.; Westall, G.P.; Kedzierska, K.; Wakim, L.M. Influenza-specific lung-resident memory T cells are proliferative and polyfunctional and maintain diverse TCR profiles. J. Clin. Investig. 2018, 128, 721-733
129. Oja, A.E.; Piet, B.; Helbig, C.; Stark, R.; van der Zwan, D.; Blaauwgeers, H.; Remmerswaal, E.B.M.; Amsen, D.; Jonkers, R.E.; Moerland, P.D.; et al. Trigger-happy resident memory CD4(+) T cells inhabit the human lungs. Mucosal Immunol.2017
130. Mackay, L.K.; Wynne-Jones, E.; Freestone, D.; Pellicci, D.G.; Mielke, L.A.; Newman, D.M.; Braun, A.; Masson, F.; Kallies, A.; Belz, G.T.; et al. T-box Transcription Factors Combine with the Cytokines TGF-beta and IL-15 to Control Tissue-Resident Memory T Cell Fate. Immunity 2015, 43, 1101-1111
131. Wakim, L.M.; Smith, J.; Caminschi, I.; Lahoud, M.H.; Villadangos, J.A. Antibody-targeted vaccination to lung dendritic cells generates tissue-resident memory CD8 T cells that are highly protective against influenza virus infection. Mucosal Immunol.2015, 8, 1060-1071
132. Zhang, N.; Bevan, M.J. Transforming Growth Factor-beta Signaling Controls the Formation and Maintenance of Gut-Resident Memory T Cells by Regulating Migration and Retention. Immunity 2013, 39, 687-696
133. + T cells. Nat. Immunol. 2013, 14, 1285-1293
134. Mackay, L.K.; Minnich, M.; Kragten, N.A.; Liao, Y.; Nota, B.; Seillet, C.; Zaid, A.; Man, K.; Preston, S.; Freestone, D.; et al. Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes. Science 2016, 352, 459-463
135. + T cells at the site of tissue regeneration enable CD69-independent maintenance. J. Exp. Med. 2016, 213, 3057-3073
136. Wakim, L.M.; Gupta, N.; Mintern, J.D.; Villadangos, J.A. Enhanced survival of lung tissue-resident memory CD8(+) T cells during infection with influenza virus due to selective expression of IFITM3. Nat. Immunol. 2013, 14, 238-245
137. Wakim, L.M.; Woodward-Davis, A.; Bevan, M.J. Memory T cells persisting within the brain after local infection show functional adaptations to their tissue of residence. Proc. Natl. Acad. Sci. USA 2010, 107, 17872-17879
138. Shin, H.; Iwasaki, A. A Vaccine strategy that protects against genital herpes by establishing local memory T cells. Nature 2012, 491, 463-467
139. Gilchuk, P.; Hill, T.M.; Guy, C.; McMaster, S.R.; Boyd, K.L.; Rabacal, W.A.; Lu, P.; Shyr, Y.; Kohlmeier, J.E.; Sebzda, E.; et al. A Distinct Lung-Interstitium-Resident Memory CD8(+) T Cell Subset Confers Enhanced Protection to Lower Respiratory Tract Infection. Cell Rep. 2016, 16, 1800-1809
140. + T cells for long-term pulmonary protection against influenza. Eur. J. Immunol. 2006, 36, 770-778
141. Gasper, D.J.; Neldner, B.; Plisch, E.H.; Rustom, H.; Carrow, E.; Imai, H.; Kawaoka, Y.; Suresh, M. Effective Respiratory CD8 T-Cell Immunity to Influenza Virus Induced by Intranasal Carbomer-Lecithin-Adjuvanted Non-replicating Vaccines. PLoS Pathog. 2016, 12, e1006064
142. + T cells in the upper respiratory tract prevent pulmonary influenza virus infection. Sci. Immunol. 2017, 2
143. Zens, K.D.; Chen, J.K.; Farber, D.L. Vaccine-generated lung tissue-resident memory T cells provide heterosubtypic protection to influenza infection. JCI Insight 2016, 1
144. Slutter, B.; Van Braeckel-Budimir, N.; Abboud, G.; Varga, S.M.; Salek-Ardakani, S.; Harty, J.T. Dynamics of influenza-induced lung-resident memory T cells underlie waning heterosubtypic immunity. Sci. Immunol. 2017, 2
145. Akondy, R.S.; Fitch, M.; Edupuganti, S.; Yang, S.; Kissick, H.T.; Li, K.W.; Youngblood, B.A.; Abdelsamed, H.A.; McGuire, D.J.; Cohen, K.W.; et al. Origin and differentiation of human memory CD8 T cells after vaccination. Nature 2017, 552, 362
146. IPD-IMGT/HLA. IMGT/HLA Statistics. 2017. Available online: https://www.ebi.ac.uk/ipd/imgt/hla/stats.html (accessed on 22 December 2017).
147. + T cell precursor frequency and subsequent effector function. J. Immunol. 2011, 186, 6319-6328
148. Keskin, D.B.; Reinhold, B.B.; Zhang, G.L.; Ivanov, A.R.; Karger, B.L.; Reinherz, E.L. Physical detection of influenza A epitopes identifies a stealth subset on human lung epithelium evading natural CD8 immunity. Proc. Natl. Acad. Sci. USA 2015, 112, 2151-2156
149. Wahl, A.; Schafer, F.; Bardet, W.; Buchli, R.; Air, G.M.; Hildebrand, W.H. HLA class I molecules consistently present internal influenza epitopes. Proc. Natl. Acad. Sci. USA 2009, 106, 540-545
150. NCBI. dbMHC Anthropology. Available online: https://www.ncbi.nlm.nih.gov/gv/mhc/ihwg.cgi?cmd=page&page=AnthroMain (accessed on 22 December 2017).
151. Hertz, T.; Oshansky, C.M.; Roddam, P.L.; DeVincenzo, J.P.; Caniza, M.A.; Jojic, N.; Mallal, S.; Phillips, E.; James, I.; Halloran, M.E.; et al. HLA targeting efficiency correlates with human T-cell response magnitude and with mortality from influenza A infection. Proc. Natl. Acad. Sci. USA 2013, 110, 13492-13497
152. Gonzalez-Galarza, F.F.; Takeshita, L.Y.; Santos, E.J.; Kempson, F.; Maia, M.H.; da Silva, A.L.; Teles e Silva, A.L.; Ghattaoraya, G.S.; Alfirevic, A.; Jones, A.R.; et al. Allele frequency net 2015 update: New features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations. Nucleic Acids Res. 2015, 43, D784-D788
153. Clemens, E.B.; Grant, E.J.; Wang, Z.; Gras, S.; Tipping, P.; Rossjohn, J.; Miller, A.; Tong, S.Y.; Kedzierska, K. Towards identification of immune and genetic correlates of severe influenza disease in Indigenous Australians. Immunol. Cell Biol. 2016, 94, 367-377
154. Tsuji, S.; Munkhbat, B.; Hagihara, M.; Tsuritani, I.; Abe, H.; Tsuji, K. HLA-A*24-B*07-DRB1*01 haplotype implicated with genetic disposition of peak bone mass in healthy young Japanese women. Hum. Immunol. 1998, 59, 243-249
155. Qu, H.Q.; Polychronakos, C. The effect of the MHC locus on autoantibodies in type 1 diabetes. J. Med. Genet. 2009, 46, 469-471
156. Chen, L.; Magliano, D.J.; Zimmet, P.Z. The worldwide epidemiology of type 2 diabetes mellitus—Present and future perspectives. Nat. Rev. Endocrinol. 2011, 8, 228-236
157. Carrington, M.; O’Brien, S.J. The influence of HLA genotype on AIDS. Annu. Rev. Med. 2003, 54, 535-551
158. Kiepiela, P.; Leslie, A.J.; Honeyborne, I.; Ramduth, D.; Thobakgale, C.; Chetty, S.; Rathnavalu, P.; Moore, C.; Pfafferott, K.J.; Hilton, L.; et al. Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA. Nature 2004, 432, 769-775
159. + T cell response in mediating HCV clearance and evolution. Hepatology 2006, 43, 563-572
160. Goulder, P.J.; Walker, B.D. HIV and HLA class I: An evolving relationship. Immunity 2012, 37, 426-440
161. Centers for Disease Control and Prevention. Deaths related to 2009 pandemic influenza A (H1N1) among American Indian/Alaska Natives—12 States, 2009. MMWR 2009, 58, 1341-1344
162. Flint, S.M.; Davis, J.S.; Su, J.Y.; Oliver-Landry, E.P.; Rogers, B.A.; Goldstein, A.; Thomas, J.H.; Parameswaran, U.; Bigham, C.; Freeman, K.; et al. Disproportionate impact of pandemic (H1N1) 2009 influenza on Indigenous people in the Top End of Australia’s Northern Territory. Med. J. Aust. 2010, 192, 617-622
163. Investigators, A.I.; Webb, S.A.; Pettila, V.; Seppelt, I.; Bellomo, R.; Bailey, M.; Cooper, D.J.; Cretikos, M.; Davies, A.R.; Finfer, S.; et al. Critical care services and 2009 H1N1 influenza in Australia and New Zealand. N. Engl. J. Med. 2009, 361, 1925-1934
164. Kumar, A.; Zarychanski, R.; Pinto, R.; Cook, D.J.; Marshall, J.; Lacroix, J.; Stelfox, T.; Bagshaw, S.; Choong, K.; Lamontagne, F.; et al. Critically ill patients with 2009 influenza A(H1N1) infection in Canada. JAMA 2009, 302, 1872-1879
165. La Ruche, G.; Tarantola, A.; Barboza, P.; Vaillant, L.; Gueguen, J.; Gastellu-Etchegorry, M.; Epidemic Intelligence Team at In VS. The 2009 pandemic H1N1 influenza and indigenous populations of the Americas and the Pacific. EuroSurveillance 2009, 14, 19366
166. Darrah, P.A.; Patel, D.T.; De Luca, P.M.; Lindsay, R.W.; Davey, D.F.; Flynn, B.J.; Hoff, S.T.; Andersen, P.; Reed, S.G.; Morris, S.L.; et al. Multifunctional TH1 cells define a correlate of Vaccine-mediated protection against Leishmania major. Nat. Med.2007, 13, 843-850
167. + T cells. J. Virol. 2008, 82, 4102-4114
168. Harari, A.; Cellerai, C.; Bellutti Enders, F.; Kostler, J.; Codarri, L.; Tapia, G.; Boyman, O.; Castro, E.; Gaudieri, S.; James, I.; et al. Skewed association of polyfunctional antigen-specific CD8 T cell populations with HLA-B genotype. Proc. Natl. Acad. Sci. USA 2007, 104, 16233-16238
169. Boon, A.C.; de Mutsert, G.; Graus, Y.M.; Fouchier, R.A.; Sintnicolaas, K.; Osterhaus, A.D.; Rimmelzwaan, G.F. The magnitude and specificity of influenza A virus-specific cytotoxic T-lymphocyte responses in humans is related to HLA-A and -B phenotype. J. Virol. 2002, 76, 582-590
170. Burrows, S.R.; Silins, S.L.; Moss, D.J.; Khanna, R.; Misko, I.S.; Argaet, V.P. T cell receptor repertoire for a viral epitope in humans is diversified by tolerance to a background major histocompatibility complex antigen. J. Exp. Med. 1995, 182, 1703-1715
171. Deng, H.; Apple, R.; Clare-Salzler, M.; Trembleau, S.; Mathis, D.; Adorini, L.; Sercarz, E. Determinant capture as a possible mechanism of protection afforded by major histocompatibility complex class II molecules in autoimmune disease. J. Exp. Med. 1993, 178, 1675-1680
172. O’Neill, H.C.; McKenzie, I.F. Quantitative variation in H-2-antigen expression. I. Estimation of H-2K and H-2D expression in different strains of mice. Immunogenetics 1980, 11, 225-239
173. Rowland-Jones, S.L.; Powis, S.H.; Sutton, J.; Mockridge, I.; Gotch, F.M.; Murray, N.; Hill, A.B.; Rosenberg, W.M.; Trowsdale, J.; McMichael, A.J. An antigen processing polymorphism revealed by HLA-B8-restricted cytotoxic T lymphocytes which does not correlate with TAP gene polymorphism. Eur. J. Immunol. 1993, 23, 1999-2004
174. Tourdot, S.; Gould, K.G. Competition between MHC class I alleles for cell surface expression alters CTL responses to influenza A virus. J. Immunol. 2002, 169, 5615-5621
175. Tussey, L.G.; Rowland-Jones, S.; Zheng, T.S.; Androlewicz, M.J.; Cresswell, P.; Frelinger, J.A.; McMichael, A.J. Different MHC class I alleles compete for presentation of overlapping viral epitopes. Immunity 1995, 3, 65-77
176. Valkenburg, S.A.; Gras, S.; Guillonneau, C.; Hatton, L.A.; Bird, N.A.; Twist, K.A.; Halim, H.; Jackson, D.C.; Purcell, A.W.; Turner, S.J.; et al. Preemptive priming readily overcomes structure-based mechanisms of virus escape. Proc. Natl. Acad. Sci. USA 2013, 110, 5570-5575
177. + T Cells Is Determined by Extraepitopic Amino Acid Residues. J. Virol. 2015, 90, 1009-1022
178. Van de Sandt, C.E.; Kreijtz, J.H.; Rimmelzwaan, G.F. Evasion of influenza A viruses from innate and adaptive immune responses. Viruses 2012, 4, 1438-1476
179. Voeten, J.T.; Bestebroer, T.M.; Nieuwkoop, N.J.; Fouchier, R.A.; Osterhaus, A.D.; Rimmelzwaan, G.F. Antigenic drift in the influenza A virus (H3N2) nucleoprotein and escape from recognition by cytotoxic T lymphocytes. J. Virol. 2000, 74, 6800-6807
180. + T cell antigenic peptides. Nat. Commun. 2013, 4, 2663
181. Berkhoff, E.G.; Boon, A.C.; Nieuwkoop, N.J.; Fouchier, R.A.; Sintnicolaas, K.; Osterhaus, A.D.; Rimmelzwaan, G.F. A mutation in the HLA-B*2705-restricted NP383-391 epitope affects the human influenza A virus-specific cytotoxic T-lymphocyte response in vitro. J. Virol. 2004, 78, 5216-5222
182. + T-cell clones. J. Gen. Virol. 2007, 88, 530-535
183. Price, G.E.; Ou, R.; Jiang, H.; Huang, L.; Moskophidis, D. Viral escape by selection of cytotoxic T cell-resistant variants in influenza A virus pneumonia. J. Exp. Med. 2000, 191, 1853-1867
184. Rimmelzwaan, G.F.; Boon, A.C.; Voeten, J.T.; Berkhoff, E.G.; Fouchier, R.A.; Osterhaus, A.D. Sequence variation in the influenza A virus nucleoprotein associated with escape from cytotoxic T lymphocytes. Virus Res. 2004, 103, 97-100
185. + T cells recognising mutant viral epitopes depends on peptide-MHC-I structural interactions and T cell activation threshold. PLoS Pathog. 2010, 6, e1001039
186. + T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses. Proc. Natl. Acad. Sci. USA 2010, 107, 12599-12604
187. Berkhoff, E.G.; Geelhoed-Mieras, M.M.; Verschuren, E.J.; van Baalen, C.A.; Gruters, R.A.; Fouchier, R.A.; Osterhaus, A.D.; Rimmelzwaan, G.F. The loss of immunodominant epitopes affects interferon-gamma production and lytic activity of the human influenza virus-specific cytotoxic T lymphocyte response in vitro. Clin. Exp. Immunol. 2007, 148, 296-306
188. Berkhoff, E.G.; de Wit, E.; Geelhoed-Mieras, M.M.; Boon, A.C.; Symons, J.; Fouchier, R.A.; Osterhaus, A.D.; Rimmelzwaan, G.F. Functional constraints of influenza A virus epitopes limit escape from cytotoxic T lymphocytes. J. Virol. 2005, 79, 11239-11246
189. Wahl, A.; McCoy, W.; Schafer, F.; Bardet, W.; Buchli, R.; Fremont, D.H.; Hildebrand, W.H. T-cell tolerance for variability in an HLA class I-presented influenza A virus epitope. J. Virol. 2009, 83, 9206-9214
190. Kiseleva, I.; Larionova, N.; Rudenko, L. Live Attenuated Reassortant Vaccines Based on A/Leningrad/134/17/57 Master Donor Virus Against H5 Avian Influenza. Open Microbiol. J. 2017, 11, 316-329
191. + T cells in pediatric HIV cure strategies after widespread early viral escape. J. Exp. Med. 2017, 214, 3239-3261
192. Ahmed, R.; Oldstone, M.B.; Palese, P. Protective immunity and susceptibility to infectious diseases: Lessons from the 1918 influenza pandemic. Nat. Immunol. 2007, 8, 1188-1193
193. WHO. WHO Recommendations on the Composition of Influenza Virus Vaccines. Available online: http://www.who.int/influenza/Vaccines/virus/recommendations/en/ (accessed on 20 November 2017).
194. Lillie, P.J.; Berthoud, T.K.; Powell, T.J.; Lambe, T.; Mullarkey, C.; Spencer, A.J.; Hamill, M.; Peng, Y.; Blais, M.E.; Duncan, C.J.; et al. Preliminary assessment of the efficacy of a T-cell-based influenza Vaccine, MVA-NP+M1, in humans. Clin. Infect. Dis. 2012, 55, 19-25
195. Giarola-Silva, S.; Coelho-Dos-Reis, J.G.A.; Mourao, M.M.; Campi-Azevedo, A.C.; Nakagaki Silva, E.E.; Luiza-Silva, M.; Martins, M.A.; Silveira-Cassette, A.C.O.; Batista, M.A.; Peruhype-Magalhaes, V.; et al. Distinct patterns of cellular immune response elicited by influenza non-adjuvanted and AS03-adjuvanted monovalent H1N1(pdm09) Vaccine. Antivir. Res. 2017, 144, 70-82
196. O’Hagan, D.T.; Rappuoli, R.; De Gregorio, E.; Tsai, T.; Del Giudice, G. MF59 adjuvant: The best insurance against influenza strain diversity. Expert Rev Vaccines 2011, 10, 447-462
197. + T-cell response with AS03-adjuvantation of a trivalent influenza Vaccine in a randomised trial of adults aged 65 and older. BMC Infect. Dis. 2014, 14, 425
198. Kumar, A.; McElhaney, J.E.; Walrond, L.; Cyr, T.D.; Merani, S.; Kollmann, T.R.; Halperin, S.A.; Scheifele, D.W. Cellular immune responses of older adults to four influenza Vaccines: Results of a randomized, controlled comparison. Hum. Vaccines Immunother. 2017, 13, 2048-2057
199. Krammer, F. Strategies to induce broadly protective antibody responses to viral glycoproteins. Expert Rev. Vaccines 2017, 16, 503-513
200. Corti, D.; Suguitan, A.L., Jr.; Pinna, D.; Silacci, C.; Fernandez-Rodriguez, B.M.; Vanzetta, F.; Santos, C.; Luke, C.J.; Torres-Velez, F.J.; Temperton, N.J.; et al. Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza Vaccine. J. Clin. Investig. 2010, 120, 1663-1673
201. Bolton, K.J.; McCaw, J.M.; Brown, L.; Jackson, D.; Kedzierska, K.; McVernon, J. Prior population immunity reduces the expected impact of CTL-inducing Vaccines for pandemic influenza control. PLoS ONE 2015, 10, e0120138
202. Zacour, M.; Ward, B.J.; Brewer, A.; Tang, P.; Boivin, G.; Li, Y.; Warhuus, M.; McNeil, S.A.; LeBlanc, J.J.; Hatchette, T.F.; et al. Standardization of Hemagglutination Inhibition Assay for Influenza Serology Allows for High Reproducibility between Laboratories. Clin. Vaccines Immunol. 2016, 23, 236-342
203. Pavlova, S.; D’Alessio, F.; Houard, S.; Remarque, E.J.; Stockhofe, N.; Engelhardt, O.G. Workshop report: Immunoassay standardisation for “universal” influenza Vaccines. Influenza Other Respir. Viruses 2017, 11, 194-201