Developing universal influenza vaccines: Hitting the nail, not just on the head

Vaccines

Volumn 3, Issue 2, 2015, Pages 239-262

  Wiersma, Lidewij C M ^a   Rimmelzwaan, Guus F ^a   de Vries, Rory D ^a  

^a ERASMUS MEDICAL CENTER   (Netherlands)

Author keywords

Influenza; MVA; Universal vaccine

Indexed keywords

DNA VACCINE; HEMAGGLUTININ; IMMUNOLOGICAL ADJUVANT; INFLUENZA VACCINE; NUCLEOPROTEIN; PROTEIN M2; SIALIDASE; VIROSOME; VIRUS VECTOR;

CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; HUMAN; HUMORAL IMMUNITY; IMMUNE RESPONSE; IMMUNOGENICITY; INFLUENZA; INFLUENZA VIRUS A; INFLUENZA VIRUS B; NONHUMAN; PUBLIC HEALTH; REVIEW; VACCINE PRODUCTION; VIRUS ATTACHMENT; VIRUS GENOME; VIRUS ISOLATION; VIRUS LIKE AGENT; VIRUS NEUTRALIZATION; VIRUS STRAIN;

EID: 85016901093     PISSN: None     EISSN: 2076393X     Source Type: Journal    
DOI: 10.3390/vaccines3020239     Document Type: Review

References (156)

1. Palese, P.S.; Shaw, M.L. Orthomyxoviridae: The viruses and their replication. In Fields Virology, 5th ed.; Lippincott Williams & Wilkins: Philadelphia, PA, USA, 2007; Volume 2, pp. 1647–1689.
2. Vijaykrishna, D.; Holmes, E.C.; Joseph, U.; Fourment, M.; Su, Y.C.; Halpin, R.; Lee, R.T.; Deng, Y.M.; Gunalan, V.; Lin, X.; et al. The contrasting phylodynamics of human influenza B viruses. eLife 2015, 4, e05055
3. Dykes, A.C.; Cherry, J.D.; Nolan, C.E. A clinical, epidemiologic, serologic, and virologic study of influenza C virus infection. Arch Intern Med. 1980, 140, 1295–1298.
4. Matsuzaki, Y.; Katsushima, N.; Nagai, Y.; Shoji, M.; Itagaki, T.; Sakamoto, M.; Kitaoka, S.; Mizuta, K.; Nishimura, H. Clinical features of influenza C virus infection in children. J Infect Dis 2006, 193, 1229–1235.
5. Molinari, N.A.; Ortega-Sanchez, I.R.; Messonnier, M.L.; Thompson, W.W.; Wortley, P.M.; Weintraub, E.; Bridges, C.B. The annual impact of seasonal influenza in the US: Measuring disease burden and costs. Vaccine 2007, 25, 5086–5096.
6. Neumann, G.; Noda, T.; Kawaoka, Y. Emergence and pandemic potential of swine-origin H1N1 influenza virus. Nature 2009, 459, 931–939.
7. Van Kerkhove, M.D.; Mumford, E.; Mounts, A.W.; Bresee, J.; Ly, S.; Bridges, C.B.; Otte, J. Highly pathogenic avian influenza (H5N1): Pathways of exposure at the animal-human interface, a systematic review. PLOS ONE 2011, 6, e14582.
8. Imai, M.; Herfst, S.; Sorrell, E.M.; Schrauwen, E.J.; Linster, M.; de Graaf, M.; Fouchier, R.A.; Kawaoka, Y. Transmission of influenza A/H5N1 viruses in mammals. Virus Res. 2013, 178, 15–20.
9. Liu, J.; Xiao, H.; Wu, Y.; Liu, D.; Qi, X.; Shi, Y.; Gao, G.F. H7N9: A low pathogenic avian influenza A virus infecting humans. Curr Opin Virol 2014, 5, 91–97.
10. Choi, Y.K.; Ozaki, H.; Webby, R.J.; Webster, R.G.; Peiris, J.S.; Poon, L.; Butt, C.; Leung, Y.H.; Guan, Y. Continuing evolution of H9N2 influenza viruses in Southeastern China. J Virol. 2004, 78, 8609–8614.
11. Wei, S.H.; Yang, J.R.; Wu, H.S.; Chang, M.C.; Lin, J.S.; Lin, C.Y.; Liu, Y.L.; Lo, Y.C.; Yang, C.H.; Chuang, J.H.; et al. Human infection with avian influenza A H6N1 virus: An epidemiological analysis. Lancet Respir Med. 2013, 1, 771–778.
12. Lopez-Martinez, I.; Balish, A.; Barrera-Badillo, G.; Jones, J.; Nunez-Garcia, T.E.; Jang, Y.; Aparicio-Antonio, R.; Azziz-Baumgartner, E.; Belser, J.A.; Ramirez-Gonzalez, J.E.; et al. Highly pathogenic avian influenza A(H7N3) virus in poultry workers, Mexico, 2012. Emerg Infect Dis. 2013, 19, 1531–1534.
13. Tweed, S.A.; Skowronski, D.M.; David, S.T.; Larder, A.; Petric, M.; Lees, W.; Li, Y.; Katz, J.; Krajden, M.; Tellier, R.; et al. Human illness from avian influenza H7N3, British Columbia. Emerg Infect Dis 2004, 10, 2196–2199.
14. Ma, C.; Lam, T.T.; Chai, Y.; Wang, J.; Fan, X.; Hong, W.; Zhang, Y.; Li, L.; Liu, Y.; Smith, D.K.; et al. Emergence and evolution of H10 subtype influenza viruses in poultry in China. J Virol. 2015, doi:10.1128/JVI.03167-14.
15. Richard, M.; de Graaf, M.; Herfst, S. Avian influenza A viruses: From zoonosis to pandemic. Future Virol. 2014, 9, 513–524.
16. Herfst, S.; Schrauwen, E.J.; Linster, M.; Chutinimitkul, S.; de Wit, E.; Munster, V.J.; Sorrell, E.M.; Bestebroer, T.M.; Burke, D.F.; Smith, D.J.; et al. Airborne transmission of influenza A/H5N1 virus between ferrets. Science 2012, 336, 1534–1541.
17. Linster, M.; van Boheemen, S.; de Graaf, M.; Schrauwen, E.J.; Lexmond, P.; Manz, B.; Bestebroer, T.M.; Baumann, J.; van Riel, D.; Rimmelzwaan, G.F.; et al. Identification, characterization, and natural selection of mutations driving airborne transmission of A/H5N1 virus. Cell 2014, 157, 329–339.
18. Imai, M.; Watanabe, T.; Hatta, M.; Das, S.C.; Ozawa, M.; Shinya, K.; Zhong, G.; Hanson, A.; Katsura, H.; Watanabe, S.; et al. Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature 2012, 486, 420–428.
19. Russell, C.A.; Fonville, J.M.; Brown, A.E.; Burke, D.F.; Smith, D.L.; James, S.L.; Herfst, S.; van Boheemen, S.; Linster, M.; Schrauwen, E.J.; et al. The potential for respiratory droplet-transmissible A/H5N1 influenza virus to evolve in a mammalian host. Science 2012, 336, 1541–1547.
20. Herfst, S.; Imai, M.; Kawaoka, Y.; Fouchier, R.A. Avian influenza virus transmission to mammals. Curr Top Microbiol Immunol. 2014, 385, 137–155.
21. Fiore, A.E.; Bridges, C.B.; Cox, N.J. Seasonal influenza vaccines. Curr Top Microbiol Immunol. 2009, 333, 43–82.
22. Smith, D.J.; Lapedes, A.S.; de Jong, J.C.; Bestebroer, T.M.; Rimmelzwaan, G.F.; Osterhaus, A.D.; Fouchier, R.A. Mapping the antigenic and genetic evolution of influenza virus. Science 2004, 305, 371–376.
23. Ampofo, W.K.; Baylor, N.; Cobey, S.; Cox, N.J.; Daves, S.; Edwards, S.; Ferguson, N.; Grohmann, G.; Hay, A.; Katz, J.; et al. Improving influenza vaccine virus selection: Report of a WHO informal consultation held at WHO headquarters, Geneva, Switzerland, 14–16 June 2010. Influenza Other Respir Viruses 2012, 6, 142–152, e1–e5.
24. Tricco, A.C.; Chit, A.; Soobiah, C.; Hallett, D.; Meier, G.; Chen, M.H.; Tashkandi, M.; Bauch, C.T.; Loeb, M. Comparing influenza vaccine efficacy against mismatched and matched strains: A systematic review and meta-analysis. BMC Med. 2013, doi:10.1186/1741-7015-11-153.
25. Laver, W.G.; Webster, R.G. Preparation and immunogenicity of an influenza virus hemagglutinin and neuraminidase subunit vaccine. Virology 1976, 69, 511–522.
26. Jefferson, T.; Rivetti, A.; di Pietrantonj, C.; Demicheli, V.; Ferroni, E. Vaccines for preventing influenza in healthy children. Cochrane Database Syst Rev 2012, doi:10.1002/14651858.CD004879.pub4.
27. Osterholm, M.T.; Kelley, N.S.; Sommer, A.; Belongia, E.A. Efficacy and effectiveness of influenza vaccines: A systematic review and meta-analysis. Lancet Infect Dis 2012, 12, 36–44.
28. Pfleiderer, M.; Trouvin, J.H.; Brasseur, D.; Granstrom, M.; Shivji, R.; Mura, M.; Cavaleri, M. Summary of knowledge gaps related to quality and efficacy of current influenza vaccines. Vaccine 2014, 32, 4586–4591.
29. Jefferson, T.; di Pietrantonj, C.; Rivetti, A.; Bawazeer, G.A.; al-Ansary, L.A.; Ferroni, E. Vaccines for preventing influenza in healthy adults. Cochrane Database Syst Rev 2014, doi:10.1002/14651858.CD001269.pub5.
30. Andersohn, F.; Bornemann, R.; Damm, O.; Frank, M.; Mittendorf, T.; Theidel, U. Vaccination of children with a live-attenuated, intranasal influenza vaccine—Analysis and evaluation through a Health Technology Assessment. GMS Health Technol Assess 2014, doi:10.3205/hta000119.
31. 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. 2014, doi:10.1093/infdis/jiu654.
32. 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.
33. Bodewes, R.; Fraaij, P.L.; Osterhaus, A.D.; Rimmelzwaan, G.F. Pediatric influenza vaccination: understanding the T-cell response. Expert Rev Vaccines 2012, 11, 963–971.
34. 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.
35. Carter, N.J.; Curran, M.P. Live attenuated influenza vaccine (FluMist(R); Fluenz): A review of its use in the prevention of seasonal influenza in children and adults. Drugs 2011, 71, 1591–1622.
36. Zeng, H.; Goldsmith, C.S.; Maines, T.R.; Belser, J.A.; Gustin, K.M.; Pekosz, A.; Zaki, S.R.; Katz, J.M.; Tumpey, T.M. Tropism and infectivity of influenza virus, including highly pathogenic avian H5N1 virus, in ferret tracheal differentiated primary epithelial cell cultures. J Virol. 2013, 87, 2597–2607.
37. Heiny, A.T.; Miotto, O.; Srinivasan, K.N.; Khan, A.M.; Zhang, G.L.; Brusic, V.; Tan, T.W.; August, J.T. Evolutionarily conserved protein sequences of influenza a viruses, avian and human, as vaccine targets. PLOS ONE 2007, 2, e1190.
38. Jegaskanda, S.; Reading, P.C.; Kent, S.J. Influenza-specific antibody-dependent cellular cytotoxicity: Toward a universal influenza vaccine. J Immunol. 2014, 193, 469–475.
39. Tong, S.; Li, Y.; Rivailler, P.; Conrardy, C.; Castillo, D.A.; Chen, L.M.; Recuenco, S.; Ellison, J.A.; Davis, C.T.; York, I.A.; et al. A distinct lineage of influenza A virus from bats. Proc Natl Acad Sci USA 2012, 109, 4269–4274.
40. Tong, S.; Zhu, X.; Li, Y.; Shi, M.; Zhang, J.; Bourgeois, M.; Yang, H.; Chen, X.; Recuenco, S.; Gomez, J.; et al. New world bats harbor diverse influenza A viruses. PLOS Pathog. 2013, 9, e1003657.
41. Steinhauer, D.A. Role of hemagglutinin cleavage for the pathogenicity of influenza virus. Virology 1999, 258, 1–20.
42. Wilson, I.A.; Skehel, J.J.; Wiley, D.C. Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution. Nature 1981, 289, 366–373.
43. Bianchi, E.; Liang, X.; Ingallinella, P.; Finotto, M.; Chastain, M.A.; Fan, J.; Fu, T.M.; Song, H.C.; Horton, M.S.; Freed, D.C.; et al. Universal influenza B vaccine based on the maturational cleavage site of the hemagglutinin precursor. J Virol. 2005, 79, 7380–7388.
44. Stanekova, Z.; Kiraly, J.; Stropkovska, A.; Mikuskova, T.; Mucha, V.; Kostolansky, F.; Vareckova, E. Heterosubtypic protective immunity against influenza A virus induced by fusion peptide of the hemagglutinin in comparison to ectodomain of M2 protein. Acta Virol. 2011, 55, 61–67.
45. Iba, Y.; Fujii, Y.; Ohshima, N.; Sumida, T.; Kubota-Koketsu, R.; Ikeda, M.; Wakiyama, M.; Shirouzu, M.; Okada, J.; Okuno, Y.; et al. Conserved neutralizing epitope at globular head of hemagglutinin in H3N2 influenza viruses. J Virol. 2014, 88, 7130–7144.
46. Ekiert, D.C.; Kashyap, A.K.; Steel, J.; Rubrum, A.; Bhabha, G.; Khayat, R.; Lee, J.H.; Dillon, M.A.; O'Neil, R.E.; Faynboym, A.M.; et al. Cross-neutralization of influenza A viruses mediated by a single antibody loop. Nature 2012, 489, 526–532.
47. Whittle, J.R.; Zhang, R.; Khurana, S.; King, L.R.; Manischewitz, J.; Golding, H.; Dormitzer, P.R.; Haynes, B.F.; Walter, E.B.; Moody, M.A.; et al. Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin. Proc Natl Acad Sci USA 2011, 108, 14216–14221.
48. Lee, P.S.; Yoshida, R.; Ekiert, D.C.; Sakai, N.; Suzuki, Y.; Takada, A.; Wilson, I.A. Heterosubtypic antibody recognition of the influenza virus hemagglutinin receptor binding site enhanced by avidity. Proc Natl Acad Sci USA 2012, 109, 17040–17045.
49. Nachbagauer, R.; Wohlbold, T.J.; Hirsh, A.; Hai, R.; Sjursen, H.; Palese, P.; Cox, R.J.; Krammer, F. Induction of broadly reactive anti-hemagglutinin stalk antibodies by an H5N1 vaccine in humans. J Virol. 2014, 88, 13260–13268.
50. Krammer, F.; Pica, N.; Hai, R.; Tan, G.S.; Palese, P. Hemagglutinin Stalk-Reactive Antibodies Are Boosted following Sequential Infection with Seasonal and Pandemic H1N1 Influenza Virus in Mice. J Virol. 2012, 86, 10302–10307.
51. Wrammert, J.; Koutsonanos, D.; Li, G.M.; Edupuganti, S.; Sui, J.; Morrissey, M.; McCausland, M.; Skountzou, I.; Hornig, M.; Lipkin, W.I.; et al. Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection. J Exp Med 2011, 208, 181–193.
52. Margine, I.; Hai, R.; Albrecht, R.A.; Obermoser, G.; Harrod, A.C.; Banchereau, J.; Palucka, K.; Garcia-Sastre, A.; Palese, P.; Treanor, J.J.; et al. H3N2 influenza virus infection induces broadly reactive hemagglutinin stalk antibodies in humans and mice. J Virol. 2013, 87, 4728–4737.
53. Henry Dunand, C.J.; Leon, P.E.; Kaur, K.; Tan, G.S.; Zheng, N.Y.; Andrews, S.; Huang, M.; Qu, X.; Huang, Y.; Salgado-Ferrer, M.; et al. Preexisting human antibodies neutralize recently emerged H7N9 influenza strains. J Clin Investig 2015, 125, 1255–1268.
54. Sui, J.; Hwang, W.C.; Perez, S.; Wei, G.; Aird, D.; Chen, L.M.; Santelli, E.; Stec, B.; Cadwell, G.; Ali, M.; et al. Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat Struct Mol Biol 2009, 16, 265–273.
55. Ekiert, D.C.; Bhabha, G.; Elsliger, M.A.; Friesen, R.H.; Jongeneelen, M.; Throsby, M.; Goudsmit, J.; Wilson, I.A. Antibody recognition of a highly conserved influenza virus epitope. Science 2009, 324, 246–251.
56. Ekiert, D.C.; Friesen, R.H.; Bhabha, G.; Kwaks, T.; Jongeneelen, M.; Yu, W.; Ophorst, C.; Cox, F.; Korse, H.J.; Brandenburg, B.; et al. A highly conserved neutralizing epitope on group 2 influenza A viruses. Science 2011, 333, 843–850.
57. Friesen, R.H.; Lee, P.S.; Stoop, E.J.; Hoffman, R.M.; Ekiert, D.C.; Bhabha, G.; Yu, W.; Juraszek, J.; Koudstaal, W.; Jongeneelen, M.; et al. A common solution to group 2 influenza virus neutralization. Proc Natl Acad Sci USA 2014, 111, 445–450.
58. Corti, D.; Voss, J.; Gamblin, S.J.; Codoni, G.; Macagno, A.; Jarrossay, D.; Vachieri, S.G.; Pinna, D.; Minola, A.; Vanzetta, F.; et al. A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. Science 2011, 333, 850–856.
59. Krammer, F.; Palese, P. Influenza virus hemagglutinin stalk-based antibodies and vaccines. Curr Opin Virol. 2013, 3, 521–530.
60. Steel, J.; Lowen, A.C.; Wang, T.T.; Yondola, M.; Gao, Q.; Haye, K.; Garcia-Sastre, A.; Palese, P. Influenza virus vaccine based on the conserved hemagglutinin stalk domain. mBio 2010, 1, e00018-10.
61. Margine, I.; Krammer, F.; Hai, R.; Heaton, N.S.; Tan, G.S.; Andrews, S.A.; Runstadler, J.A.; Wilson, P.C.; Albrecht, R.A.; Garcia-Sastre, A.; et al. Hemagglutinin stalk-based universal vaccine constructs protect against group 2 influenza A viruses. J Virol. 2013, 87, 10435–10446.
62. Krammer, F.; Pica, N.; Hai, R.; Margine, I.; Palese, P. Chimeric hemagglutinin influenza virus vaccine constructs elicit broadly protective stalk-specific antibodies. J Virol. 2013, 87, 6542–6550.
63. Krammer, F.; Hai, R.; Yondola, M.; Tan, G.S.; Leyva-Grado, V.H.; Ryder, A.B.; Miller, M.S.; Rose, J.K.; Palese, P.; Garcia-Sastre, A.; et al. Assessment of influenza virus hemagglutinin stalk-based immunity in ferrets. J Virol. 2014, 88, 3432–3442.
64. Mallajosyula, V.V.; Citron, M.; Ferrara, F.; Lu, X.; Callahan, C.; Heidecker, G.J.; Sarma, S.P.; Flynn, J.A.; Temperton, N.J.; Liang, X.; et al. Influenza hemagglutinin stem-fragment immunogen elicits broadly neutralizing antibodies and confers heterologous protection. Proc Natl Acad Sci USA 2014, 111, E2514–E2523.
65. Zhu, X.; Yang, H.; Guo, Z.; Yu, W.; Carney, P.J.; Li, Y.; Chen, L.M.; Paulson, J.C.; Donis, R.O.; Tong, S.; et al. Crystal structures of two subtype N10 neuraminidase-like proteins from bat influenza A viruses reveal a diverged putative active site. Proc Natl Acad Sci USA 2012, 109, 18903–18908.
66. Li, Q.; Sun, X.; Li, Z.; Liu, Y.; Vavricka, C.J.; Qi, J.; Gao, G.F. Structural and functional characterization of neuraminidase-like molecule N10 derived from bat influenza A virus. Proc Natl Acad Sci USA 2012, 109, 18897–18902.
67. Schulman, J.L.; Khakpour, M.; Kilbourne, E.D. Protective effects of specific immunity to viral neuraminidase on influenza virus infection of mice. J Virol. 1968, 2, 778–786.
68. Johansson, B.E.; Bucher, D.J.; Kilbourne, E.D. Purified influenza virus hemagglutinin and neuraminidase are equivalent in stimulation of antibody response but induce contrasting types of immunity to infection. J Virol. 1989, 63, 1239–1246.
69. Couch, R.B.; Atmar, R.L.; Keitel, W.A.; Quarles, J.M.; Wells, J.; Arden, N.; Nino, D. Randomized comparative study of the serum antihemagglutinin and antineuraminidase antibody responses to six licensed trivalent influenza vaccines. Vaccine 2012, 31, 190–195.
70. Marcelin, G.; Sandbulte, M.R.; Webby, R.J. Contribution of antibody production against neuraminidase to the protection afforded by influenza vaccines. Rev Med Virol. 2012, 22, 267–279.
71. Doyle, T.M.; Hashem, A.M.; Li, C.; van Domselaar, G.; Larocque, L.; Wang, J.; Smith, D.; Cyr, T.; Farnsworth, A.; He, R.; et al. Universal anti-neuraminidase antibody inhibiting all influenza A subtypes. Antiviral Res. 2013, 100, 567–574.
72. Doyle, T.M.; Li, C.; Bucher, D.J.; Hashem, A.M.; van Domselaar, G.; Wang, J.; Farnsworth, A.; She, Y.M.; Cyr, T.; He, R.; et al. A monoclonal antibody targeting a highly conserved epitope in influenza B neuraminidase provides protection against drug resistant strains. Biochem Biophys Res Commun. 2013, 441, 226–229.
73. Johansson, B.E.; Cox, M.M. Influenza viral neuraminidase: The forgotten antigen. Expert Rev Vaccines 2011, 10, 1683–1695.
74. Bosch, B.J.; Bodewes, R.; de Vries, R.P.; Kreijtz, J.H.; Bartelink, W.; van Amerongen, G.; Rimmelzwaan, G.F.; de Haan, C.A.; Osterhaus, A.D.; Rottier, P.J. Recombinant soluble, multimeric HA and NA exhibit distinctive types of protection against pandemic swine-origin 2009 A(H1N1) influenza virus infection in ferrets. J Virol. 2010, 84, 10366–10374.
75. Wohlbold, T.J.; Krammer, F. In the shadow of hemagglutinin: A growing interest in influenza viral neuraminidase and its role as a vaccine antigen. Viruses 2014, 6, 2465–2494.
76. Fiers, W.; de Filette, M.; el Bakkouri, K.; Schepens, B.; Roose, K.; Schotsaert, M.; Birkett, A.; Saelens, X. M2e-based universal influenza A vaccine. Vaccine 2009, 27, 6280–6283.
77. El Bakkouri, K.; Descamps, F.; de Filette, M.; Smet, A.; Festjens, E.; Birkett, A.; van Rooijen, N.; Verbeek, S.; Fiers, W.; Saelens, X. Universal vaccine based on ectodomain of matrix protein 2 of influenza A: Fc receptors and alveolar macrophages mediate protection. J Immunol. 2011, 186, 1022–1031.
78. Neirynck, S.; Deroo, T.; Saelens, X.; Vanlandschoot, P.; Jou, W.M.; Fiers, W. A universal influenza A vaccine based on the extracellular domain of the M2 protein. Nat Med. 1999, 5, 1157–1163.
79. De Filette, M.; Min Jou, W.; Birkett, A.; Lyons, K.; Schultz, B.; Tonkyro, A.; Resch, S.; Fiers, W. Universal influenza A vaccine: Optimization of M2-based constructs. Virology 2005, 337, 149–161.
80. LaMere, M.W.; Lam, H.T.; Moquin, A.; Haynes, L.; Lund, F.E.; Randall, T.D.; Kaminski, D.A. Contributions of antinucleoprotein IgG to heterosubtypic immunity against influenza virus. J Immunol. 2011, 186, 4331–4339.
81. Lamere, M.W.; Moquin, A.; Lee, F.E.; Misra, R.S.; Blair, P.J.; Haynes, L.; Randall, T.D.; Lund, F.E.; Kaminski, D.A. Regulation of antinucleoprotein IgG by systemic vaccination and its effect on influenza virus clearance. J Virol. 2011, 85, 5027–5035.
82. Bodewes, R.; Geelhoed-Mieras, M.M.; Wrammert, J.; Ahmed, R.; Wilson, P.C.; Fouchier, R.A.; Osterhaus, A.D.; Rimmelzwaan, G.F. In vitro assessment of the immunological significance of a human monoclonal antibody directed to the influenza a virus nucleoprotein. Clin Vaccine Immunol. 2013, 20, 1333–1337.
83. Virelizier, J.L.; Allison, A.C.; Oxford, J.S.; Schild, G.C. Early presence of ribonucleoprotein antigen on surface of influenza virus-infected cells. Nature 1977, 266, 52–54.
84. Laidlaw, B.J.; Decman, V.; Ali, M.A.; Abt, M.C.; Wolf, A.I.; Monticelli, L.A.; Mozdzanowska, K.; Angelosanto, J.M.; Artis, D.; Erikson, J.; et al. Cooperativity between CD8+ T cells, non-neutralizing antibodies, and alveolar macrophages is important for heterosubtypic influenza virus immunity. PLOS Pathog. 2013, 9, e1003207.
85. Carragher, D.M.; Kaminski, D.A.; Moquin, A.; Hartson, L.; Randall, T.D. A novel role for non-neutralizing antibodies against nucleoprotein in facilitating resistance to influenza virus. J Immunol. 2008, 181, 4168–4176.
86. Thomas, P.G.; Keating, R.; Hulse-Post, D.J.; Doherty, P.C. Cell-mediated protection in influenza infection. Emerg Infect Dis. 2006, 12, 48–54.
87. 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.
88. 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.
89. 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.
90. 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.
91. Grebe, K.M.; Yewdell, J.W.; Bennink, J.R. Heterosubtypic immunity to influenza A virus: Where do we stand? Microbes Infect. 2008, 10, 1024–1029.
92. 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.
93. 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.
94. Florek, N.W.; Weinfurter, J.T.; Jegaskanda, S.; Brewoo, J.N.; Powell, T.D.; Young, G.R.; Das, S.C.; Hatta, M.; Broman, K.W.; Hungnes, O.; et al. Modified vaccinia virus Ankara encoding influenza virus hemagglutinin induces heterosubtypic immunity in macaques. J Virol. 2014, 88, 13418–13428.
95. Nakayama, M.; Shichinohe, S.; Itoh, Y.; Ishigaki, H.; Kitano, M.; Arikata, M.; Pham, V.L.; Ishida, H.; Kitagawa, N.; Okamatsu, M.; et al. Protection against H5N1 highly pathogenic avian and pandemic (H1N1) 2009 influenza virus infection in cynomolgus monkeys by an inactivated H5N1 whole particle vaccine. PLOS ONE 2013, 8, e82740.
96. Wilkinson, T.M.; Li, C.K.; Chui, C.S.; Huang, A.K.; Perkins, M.; Liebner, J.C.; Lambkin-Williams, R.; Gilbert, A.; Oxford, J.; Nicholas, B.; et al. Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nat Med 2012, 18, 274–280.
97. 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.
98. 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.
99. 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.
100. Altenburg, A.F.; Rimmelzwaan, G.F.; de Vries, R.D. Virus-specific T cells as correlate of (cross-) protective immunity against influenza. Vaccine 2015, 33, 500–506.
101. Hillaire, M.L.; Osterhaus, A.D.; Rimmelzwaan, G.F. Induction of virus-specific cytotoxic T lymphocytes as a basis for the development of broadly protective influenza vaccines. J Biomed Biotechnol. 2011, doi:10.1155/2011/939860.
102. Yewdell, J.W.; Bennink, J.R.; Smith, G.L.; Moss, B. Influenza A virus nucleoprotein is a major target antigen for cross-reactive anti-influenza A virus cytotoxic T lymphocytes. Proc Natl Acad Sci USA 1985, 82, 1785–1789.
103. Zheng, M.; Luo, J.; Chen, Z. Development of universal influenza vaccines based on influenza virus M and NP genes. Infection 2014, 42, 251–262.
104. Gotch, F.; Rothbard, J.; Howland, K.; Townsend, A.; McMichael, A. Cytotoxic T lymphocytes recognize a fragment of influenza virus matrix protein in association with HLA-A2. Nature 1987, 326, 881–882.
105. Choo, J.A.; Liu, J.; Toh, X.; Grotenbreg, G.M.; Ren, E.C. The immunodominant influenza A virus M158–66 cytotoxic T lymphocyte epitope exhibits degenerate class I major histocompatibility complex restriction in humans. J Virol. 2014, 88, 10613–10623.
106. 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.
107. Collins, P.L.; Bukreyev, A.; Murphy, B.R. What are the risks—Hypothetical and observed—Of recombination involving live vaccines and vaccine vectors based on nonsegmented negative-strain RNA viruses? J Virol. 2008, 82, 9805–9806.
108. Coughlan, L.; Mullarkey, C.; Gilbert, S. Adenoviral vectors as novel vaccines for influenza. J Pharm Pharmacol. 2015, doi:10.1111/jphp.12350.
109. Dudek, T.; Knipe, D.M. Replication-defective viruses as vaccines and vaccine vectors. Virology 2006, 344, 230–239.
110. He, F.; Madhan, S.; Kwang, J. Baculovirus vector as a delivery vehicle for influenza vaccines. Expert Rev Vaccines 2009, 8, 455–467.
111. Draper, S.J.; Cottingham, M.G.; Gilbert, S.C. Utilizing poxviral vectored vaccines for antibody induction-progress and prospects. Vaccine 2013, 31, 4223–4230.
112. Price G.E.; Soboleski M.R.; Lo C.Y.; Misplon J.A.; Quirion M.R.; Houser K.V.; Pearce M.B.; Pappas C.; Tumpey T.M.; Epstein SL Single-dose mucosal immunization with a candidate universal influenza vaccine provides rapid protection from virulent H5N1 H3N2 and H1N1 viruses. PLOS ONE 2010 5
113. Price, G.E.; Lo, C.Y.; Misplon, J.A.; Epstein, S.L. Mucosal immunization with a candidate universal influenza vaccine reduces virus transmission in a mouse model. J Virol 2014, 88, 6019–6030.
114. Rimmelzwaan, G.F.; Sutter, G. Candidate influenza vaccines based on recombinant modified vaccinia virus Ankara. Expert Rev Vaccines 2009, 8, 447–454.
115. Altenburg, A.F.; Kreijtz, J.H.; de Vries, R.D.; Song, F.; Fux, R.; Rimmelzwaan, G.F.; Sutter, G.; Volz, A. Modified vaccinia virus ankara (MVA) as production platform for vaccines against influenza and other viral respiratory diseases. Viruses 2014, 6, 2735–2761.
116. Sutter, G.; Moss, B. Nonreplicating vaccinia vector efficiently expresses recombinant genes. Proc Natl Acad Sci USA 1992, 89, 10847–10851.
117. Brewoo, J.N.; Powell, T.D.; Jones, J.C.; Gundlach, N.A.; Young, G.R.; Chu, H.; Das, S.C.; Partidos, C.D.; Stinchcomb, D.T.; Osorio, J.E. Cross-protective immunity against multiple influenza virus subtypes by a novel modified vaccinia Ankara (MVA) vectored vaccine in mice. Vaccine 2013, 31, 1848–1855.
118. Kreijtz, J.H.; Suezer, Y.; de Mutsert, G.; van den Brand, J.M.; van Amerongen, G.; Schnierle, B.S.; Kuiken, T.; Fouchier, R.A.; Lower, J.; Osterhaus, A.D.; et al. Preclinical evaluation of a modified vaccinia virus Ankara (MVA)-based vaccine against influenza A/H5N1 viruses. Vaccine 2009, 27, 6296–6299.
119. Hessel, A.; Schwendinger, M.; Holzer, G.W.; Orlinger, K.K.; Coulibaly, S.; Savidis-Dacho, H.; Zips, M.L.; Crowe, B.A.; Kreil, T.R.; Ehrlich, H.J.; et al. Vectors based on modified vaccinia Ankara expressing influenza H5N1 hemagglutinin induce substantial cross-clade protective immunity. PLOS ONE 2011, 6, e16247.
120. Kreijtz, J.H.; Wiersma, L.C.; de Gruyter, H.L.; Vogelzang-van Trierum, S.E.; van Amerongen, G.; Stittelaar, K.J.; Fouchier, R.A.; Osterhaus, A.D.; Sutter, G.; Rimmelzwaan, G.F. A Single Immunization with Modified Vaccinia Virus Ankara-Based Influenza Virus H7 Vaccine Affords Protection in the Influenza A(H7N9) Pneumonia Ferret Model. J Infect Dis. 2015, 211, 791–800.
121. Hessel, A.; Schwendinger, M.; Fritz, D.; Coulibaly, S.; Holzer, G.W.; Sabarth, N.; Kistner, O.; Wodal, W.; Kerschbaum, A.; Savidis-Dacho, H.; et al. A pandemic influenza H1N1 live vaccine based on modified vaccinia Ankara is highly immunogenic and protects mice in active and passive immunizations. PLOS ONE 2010, 5, e12217.
122. Kreijtz, J.H.; Suzer, Y.; Bodewes, R.; Schwantes, A.; van Amerongen, G.; Verburgh, R.J.; de Mutsert, G.; van den Brand, J.; van Trierum, S.E.; Kuiken, T.; et al. Evaluation of a modified vaccinia virus Ankara (MVA)-based candidate pandemic influenza A/H1N1 vaccine in the ferret model. J Gen Virol 2010, 91, 2745–2752.
123. 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.
124. Lambe, T.; Carey, J.B.; Li, Y.; Spencer, A.J.; van Laarhoven, A.; Mullarkey, C.E.; Vrdoljak, A.; Moore, A.C.; Gilbert, S.C. Immunity against heterosubtypic influenza virus induced by adenovirus and MVA expressing nucleoprotein and matrix protein-1. Sci Rep. 2013, doi:10.1038/srep01443.
125. Gilbert, S.C. Clinical development of Modified Vaccinia virus Ankara vaccines. Vaccine 2013, 31, 4241–4246.
126. Kreijtz, J.H.; Goeijenbier, M.; Moesker, F.M.; van den Dries, L.; Goeijenbier, S.; de Gruyter, H.L.; Lehmann, M.H.; Mutsert, G.; van de Vijver, D.A.; Volz, A.; et al. Safety and immunogenicity of a modified-vaccinia-virus-Ankara-based influenza A H5N1 vaccine: A randomised, double-blind phase 1/2a clinical trial. Lancet Infect Dis. 2014, 14, 1196–1207.
127. Robert-Guroff, M. Replicating and non-replicating viral vectors for vaccine development. Curr Opin Biotechnol. 2007, 18, 546–556.
128. Lambe, T. Novel viral vectored vaccines for the prevention of influenza. Mol Med. 2012, 18, 1153–1160.
129. Mogler, M.A.; Kamrud, K.I. RNA-based viral vectors. Expert Rev Vaccines 2015, 14, 283–312.
130. Kim, J.H.; Jacob, J. DNA vaccines against influenza viruses. Curr Top Microbiol Immunol. 2009, 333, 197–210.
131. Khan, K.H. DNA vaccines: Roles against diseases. Germs 2013, 3, 26–35.
132. Ulmer, J.B.; Donnelly, J.J.; Parker, S.E.; Rhodes, G.H.; Felgner, P.L.; Dwarki, V.J.; Gromkowski, S.H.; Deck, R.R.; de Witt, C.M.; Friedman, A.; et al. Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 1993, 259, 1745–1749.
133. Donnelly, J.J.; Friedman, A.; Martinez, D.; Montgomery, D.L.; Shiver, J.W.; Motzel, S.L.; Ulmer, J.B.; Liu, M.A. Preclinical efficacy of a prototype DNA vaccine: Enhanced protection against antigenic drift in influenza virus. Nat Med 1995, 1, 583–587.
134. Laddy, D.J.; Yan, J.; Kutzler, M.; Kobasa, D.; Kobinger, G.P.; Khan, A.S.; Greenhouse, J.; Sardesai, N.Y.; Draghia-Akli, R.; Weiner, D.B. Heterosubtypic protection against pathogenic human and avian influenza viruses via in vivo electroporation of synthetic consensus DNA antigens. PLOS ONE 2008, 3, e2517.
135. Drape, R.J.; Macklin, M.D.; Barr, L.J.; Jones, S.; Haynes, J.R.; Dean, H.J. Epidermal DNA vaccine for influenza is immunogenic in humans. Vaccine 2006, 24, 4475–4481.
136. Jones, S.; Evans, K.; McElwaine-Johnn, H.; Sharpe, M.; Oxford, J.; Lambkin-Williams, R.; Mant, T.; Nolan, A.; Zambon, M.; Ellis, J.; et al. DNA vaccination protects against an influenza challenge in a double-blind randomised placebo-controlled phase 1b clinical trial. Vaccine 2009, 27, 2506–2512.
137. Smith, L.R.; Wloch, M.K.; Ye, M.; Reyes, L.R.; Boutsaboualoy, S.; Dunne, C.E.; Chaplin, J.A.; Rusalov, D.; Rolland, A.P.; Fisher, C.L.; et al. Phase 1 clinical trials of the safety and immunogenicity of adjuvanted plasmid DNA vaccines encoding influenza A virus H5 hemagglutinin. Vaccine 2010, 28, 2565–2572.
138. Ulmer, J.B.; Mansoura, M.K.; Geall, A.J. Vaccines “on demand”: Science fiction or a future reality. Expert Opin Drug Discov. 2015, 10, 101–106.
139. Kramps, T.; Probst, J. Messenger RNA-based vaccines: Progress, challenges, applications. Wiley Interdiscip Rev. 2013, 4, 737–749.
140. Thompson, C.M.; Petiot, E.; Lennaertz, A.; Henry, O.; Kamen, A.A. Analytical technologies for influenza virus-like particle candidate vaccines: Challenges and emerging approaches. Virol J. 2013, 10, 141.
141. Roldao, A.; Mellado, M.C.; Castilho, L.R.; Carrondo, M.J.; Alves, P.M. Virus-like particles in vaccine development. Expert Rev Vaccines 2010, 9, 1149–1176.
142. Haynes, J.R. Influenza virus-like particle vaccines. Expert Rev Vaccines 2009, 8, 435–445.
143. Kang, S.M.; Pushko, P.; Bright, R.A.; Smith, G.; Compans, R.W. Influenza virus-like particles as pandemic vaccines. Curr Top Microbiol Immunol. 2009, 333, 269–289.
144. Lopez-Macias, C. Virus-like particle (VLP)-based vaccines for pandemic influenza: Performance of a VLP vaccine during the 2009 influenza pandemic. Hum Vaccin Immunother. 2012, 8, 411–414.
145. Huckriede, A.; Bungener, L.; Stegmann, T.; Daemen, T.; Medema, J.; Palache, A.M.; Wilschut, J. The virosome concept for influenza vaccines. Vaccine 2005, 23, S26–S38.
146. Moser, C.; Muller, M.; Kaeser, M.D.; Weydemann, U.; Amacker, M., Influenza virosomes as vaccine adjuvant and carrier system. Expert Rev. Vaccines 2013, 12, 779–791.
147. Tetsutani, K.; Ishii, K.J. Adjuvants in influenza vaccines. Vaccine 2012, 30, 7658–7661.
148. Khurana, S.; Verma, N.; Yewdell, J.W.; Hilbert, A.K.; Castellino, F.; Lattanzi, M.; Del Giudice, G.; Rappuoli, R.; Golding, H. MF59 adjuvant enhances diversity and affinity of antibody-mediated immune response to pandemic influenza vaccines. Sci Transl Med 2011, doi:10.1126/scitranslmed.3002336.
149. Van Binnendijk, R.S.; van Baalen, C.A.; Poelen, M.C.; de Vries, P.; Boes, J.; Cerundolo, V.; Osterhaus, A.D.; UytdeHaag, F.G. Measles virus transmembrane fusion protein synthesized de novo or presented in immunostimulating complexes is endogenously processed for HLA class I- and class II-restricted cytotoxic T cell recognition. J Exp Med 1992, 176, 119–128.
150. Sun, H.X.; Xie, Y.; Ye, Y.P. ISCOMs and ISCOMATRIX. Vaccine 2009, 27, 4388–4401.
151. Rimmelzwaan, G.F.; Nieuwkoop, N.; Brandenburg, A.; Sutter, G.; Beyer, W.E.; Maher, D.; Bates, J.; Osterhaus, A.D. A randomized, double blind study in young healthy adults comparing cell mediated and humoral immune responses induced by influenza ISCOM vaccines and conventional vaccines. Vaccine 2000, 19, 1180–1187.
152. Van de Sandt, C.E.; Kreijtz, J.H.; Geelhoed-Mieras, M.M.; Vogelzang-van Trierum, S.E.; Nieuwkoop, N.J.; van de Vijver, D.A.; Fouchier, R.A.; Osterhaus, A.D.; Morein, B.; Rimmelzwaan, G.F. Novel G3/DT adjuvant promotes the induction of protective T cells responses after vaccination with a seasonal trivalent inactivated split-virion influenza vaccine. Vaccine 2014, 32, 5614–5623.
153. Sambhara, S.; Kurichh, A.; Miranda, R.; Tumpey, T.; Rowe, T.; Renshaw, M.; Arpino, R.; Tamane, A.; Kandil, A.; James, O.; et al. Heterosubtypic immunity against human influenza A viruses, including recently emerged avian H5 and H9 viruses, induced by FLU-ISCOM vaccine in mice requires both cytotoxic T-lymphocyte and macrophage function. Cell Immunol. 2001, 211, 143–153.
154. Li, Y.; Myers, J.L.; Bostick, D.L.; Sullivan, C.B.; Madara, J.; Linderman, S.L.; Liu, Q.; Carter, D.M.; Wrammert, J.; Esposito, S.; et al. Immune history shapes specificity of pandemic H1N1 influenza antibody responses. J Exp Med 2013, 210, 1493–1500.
155. Linderman, S.L.; Chambers, B.S.; Zost, S.J.; Parkhouse, K.; Li, Y.; Herrmann, C.; Ellebedy, A.H.; Carter, D.M.; Andrews, S.F.; Zheng, N.Y.; et al. Potential antigenic explanation for atypical H1N1 infections among middle-aged adults during the 2013–2014 influenza season. Proc Natl Acad Sci USA 2014, 111, 15798–15803.
156. Ellebedy, A.H.; Krammer, F.; Li, G.M.; Miller, M.S.; Chiu, C.; Wrammert, J.; Chang, C.Y.; Davis, C.W.; McCausland, M.; Elbein, R.; 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, 13133–13138.