Universal influenza virus vaccines: what needs to happen next?

References

• Immunization, vaccines and biologicals. influenza. [Internet]. WHO; [cited 2018 Aug 29]. Available from: www.who.int/immunization/topics/influenza/en/
   Google Scholar
• Influenza. Data and statistics [Internet]. WHO; [cited 2018 Apr 29]. Available from: www.euro.who.int/en/healthtopics/communicable-diseases/influenza/data-and-statistics
   Google Scholar
• Vasin AV, Temkina OA, Egorov VV, et al. Molecular mechanisms enhancing the proteome of influenza A viruses: an overview of recently discovered proteins. Virus Res. 2014;185:53–63.
   PubMed Web of Science ®Google Scholar
• Palese P. Influenza: old and new threats. Nat Med. 2004;10:S82–S87.
   PubMed Web of Science ®Google Scholar
• Berlanda Scorza F, Tsvetnitsky V, Donnelly JJ. Universal influenza vaccines: shifting to better vaccines. Vaccine. 2016;34(26):2926–2933.
   PubMed Web of Science ®Google Scholar
• Sautto GA, Kirchenbaum GA, Ross TM. Towards a universal influenza vaccine: different approaches for one goal. Virol J. 2018;15:17.
   PubMed Web of Science ®Google Scholar
• Tong S, Li Y, Rivailler P, et al. A distinct lineage of influenza A virus from bats. Proc Natl Acad Sci U S A. 2012;109:4269–4274.
   PubMed Web of Science ®Google Scholar
• Tong S, Zhu X, Li Y, et al. New world bats harbor diverse influenza A viruses. PLoS Pathog. 2013;9:e1003657.
   PubMed Web of Science ®Google Scholar
• Sonnberg S, Webby RJ, Webster RG. Natural history of highly pathogenic avian influenza H5N1. Virus Res. 2013;178:63–77.
   PubMed Web of Science ®Google Scholar
• White JM, Hoffman LR, Arevalo JH, et al. Attachment and entry of influenza virus into host cells. Pivotal roles of hemagglutinin. In: Chiu W, Burnett RM, Garcea RL editors. Structural biology of viruses. New York (NY): Oxford University Press; 1997. p. 80–104.
   Google Scholar
• Matrosovich M, Matrosovich T, Gray T, et al. Neuraminidase is important for the initiation of influenza virus infection in human airway epitelium. J Virol. 2004;78:12665–12667.
   PubMed Web of Science ®Google Scholar
• Wagner R, Wolf T, Herwig A, et al. Interdependence of hemagglutinin glycosylation and neuraminidase as regulators of influenza growth: a study by reverse genetics. J Virol. 2000;74:6316–6323.
   PubMed Web of Science ®Google Scholar
• Schulman JL, Khakpour M, Kilbourne ED. Protective effects of specific immunity to viral neuraminidase on influenza virus infection of mice. J Virol. 1968;2(8):778–786.
   PubMed Web of Science ®Google Scholar
• McLaren C, Potter CW, Jennings R. Immunity to influenza in ferrets XIII. Protection against influenza infection by serum antibody to homologous haemagglutinin or neuraminidase antigens. Med Microbiol Immunol Infect Immun. 1974;160:33–45.
   PubMed Web of Science ®Google Scholar
• Ramilo O, Rodriguez-Fernandez R, Mejias A. One step forward in the road toward a universal influenza vaccine. J Infect Dis. 2017;217:1–2.
   PubMed Web of Science ®Google Scholar
• Kilbourne ED. Influenza pandemics of the 20th century. Emerg Infect Dis. 2006;12:9–14.
   PubMed Web of Science ®Google Scholar
• Wohlbold TJ, Krammer F. In the shadow of hemagglutinin: a growing interest in influenza viral neuraminidase and its role as a vaccine antigen. Viruses. 2014;6(6):2465–2494.
   PubMed Web of Science ®Google Scholar
• Cohen M, Zhang XQ, Senaati HP, et al. Influenza A penetrates host mucus by cleaving sialic acids with neuraminidase. Virol J. 2013;10:321.
   PubMed Web of Science ®Google Scholar
• Beigel JH, Farrar J, Han AM, et al. Avian influenza A (H5N1) infection in humans. N Engl J Med. 2005;353:1374–1385.
   PubMed Web of Science ®Google Scholar
• Tanner WD, Toth DJ, Gundlapalli AV. The pandemic potential of avian influenza A(H7N9) virus: a review. Epidemiol Infect. 2015;143:3359–3374.
   PubMed Web of Science ®Google Scholar
• Rota PA, Wallis TR, Harmon MW, et al. Cocirculation of two distinct evolutionary lineages of influenza type B virus since 1983. Virology. 1990;175:59–68.
   PubMed Web of Science ®Google Scholar
• Biere B, Bauer B, Schweiger B. Differentiation of influenza B virus lineages Yamagata and Victoria by real-time PCR. J Clin Microbiol. 2010;48:1425–1427.
   PubMed Web of Science ®Google Scholar
• Hause BM, Collin EA, Liu R, et al. Characterization of a novel influenza virus in cattle and swine: proposal for a new genus in the Orthomyxoviridae family. MBio. 2014;5:e00031–14.
   PubMed Web of Science ®Google Scholar
• Webster RG, Govorkova EA. Continuing challenges in influenza. Ann NY Acad Sci. 2014;1323:115–139.
   PubMed Web of Science ®Google Scholar
• Fitch WM, Leiter JM, Li XQ, et al. Positive Darwinian evolution in human influenza A viruses. Proc Natl Acad Sci U S A. 1991;88:4270–4274.
   PubMed Web of Science ®Google Scholar
• Koelle K, Cobey S, Grenfell B, et al. Epochal evolution shapes the phylodynamics of interpandemic influenza A (H3N2) in humans. Science. 2006;314:1898–1903.
   PubMed Web of Science ®Google Scholar
• Treanor J. Influenza vaccine-outmaneuvering antigenic shift and drift. N Engl J Med. 2004;350:218–220.
   PubMed Web of Science ®Google Scholar
• Szewczyk B, Bieńkowska-Szewczyk K, Król E. Introduction to molecular biology of influenza a viruses. Acta Biochim Pol. 2014;61:397–401.
   PubMed Web of Science ®Google Scholar
• Smith DJ, Lapedes AS, de Jong JC, et al. Mapping the antigenic and genetic evolution of influenza virus. Science. 2004;305:371–376.
   PubMed Web of Science ®Google Scholar
• Seasonal overviews of influenza in Europe [Internet]. ECDC; [cited 2018 Jun 15]. Available from: ecdc.europa.eu/en/seasonal-influenza/surveillance-and-disease-data/seasonal-overviews
   Google Scholar
• Seasonal influenza. Flu activity & surveillance [Internet]. CDC; [cited 2018 Oct 15]. Available from: www.cdc.gov/flu/weekly/pastreports.htm
   Google Scholar
• Recommendations on the composition of influenza virus vaccines [Internet]. WHO; [cited 2018 Jan 15]. Available from: www.who.int/influenza/vaccines/virus/recommendations/en/
   Google Scholar
• Moa AM, Muscatello DJ, Turner RM, et al. Epidemiology of influenza B in Australia: 2001‐2014 influenza seasons. Influenza Other Respir Virus. 2017;11:102–109.
   PubMed Web of Science ®Google Scholar
• Trucchi C, Alicino C, Orsi A, et al. Fifteen years of epidemiologic, virologic and syndromic influenza surveillance: A focus on type B virus and the effects of vaccine mismatch in Liguria region, Italy. Hum Vaccin Immunother. 2017;13:456–463.
   PubMed Web of Science ®Google Scholar
• Webster RG, Laver WG, Air GM, et al. Molecular mechanisms of variation in influenza viruses. Nature. 1982;296:115–121.
   PubMed Web of Science ®Google Scholar
• Cox NJ, Subbarao K. Global epidemiology of influenza: past and present. Annu Rev Med. 2000;51:407–421.
   PubMed Web of Science ®Google Scholar
• Webster RG, Bean WJ, Gorman OT, et al. Evolution and ecology of influenza A viruses. Microbiol Rev. 1994;56:152–179.
   Google Scholar
• Burnet FM, Lind PE. A genetic approach to variation in influenza viruses; recombination of characters in influenza virus strains used in mixed infections. J Gen Microbiol. 1951;5:59–66.
   PubMedGoogle Scholar
• Hirst GK, Gotlieb T. The experimental production of combination forms of virus. I. Occurrence of combination forms after simultaneous inoculation of the allantoic sac with two distinct strains of influenza virus. J Exp Med. 1953;98:41–52.
   PubMed Web of Science ®Google Scholar
• Parrish CR, Murcia PR, Holmes EC. Influenza virus reservoirs and intermediate hosts: dogs, horses, and new possibilities for influenza virus exposure of humans. J Virol. 2015;89:2990–2994.
   PubMed Web of Science ®Google Scholar
• Ma W, Kahn RE, Richt JA. The pig as a mixing vessel for influenza viruses: human and veterinary implications. J Mol Genet Med. 2008;3:158–166.
   PubMedGoogle Scholar
• Garten RJ. Antigenic and genetic characteristics of swineorigin 2009 A(H1N1) influenza viruses circulating in humans. Science. 2009;325:197–201.
   PubMed Web of Science ®Google Scholar
• Ilyushina NA, Kim JK, Negovetich NJ, et al. Extensive mammalian ancestry of pandemic (H1N1) 2009 virus. Emerg Infect Dis. 2010;16:314–317.
   PubMed Web of Science ®Google Scholar
• Ambrose CS, Levin MJ. The rationale for quadrivalent influenza vaccines. Hum Vaccin Immunother. 2012;8:81–88.
   PubMed Web of Science ®Google Scholar
• Gasparini R, Amicizia D, Lai PL, et al. Live attenuated influenza vaccine – a review. J Prev Med Hyg. 2011;52(3):95–101. 13. Fiore AE, Bridges CB, Cox NJ. Seasonal influenza vaccines. Curr Top Microbiol Immunol 2009;333:43–82.
   PubMedGoogle Scholar
• Manini I, Domnich A, Amicizia D, et al. Flucelvax (Optaflu) for seasonal influenza. Expert Rev Vaccines. 2015;14:789–804.
   PubMed Web of Science ®Google Scholar
• Cox MM, Izikson R, Post P, et al. Safety, efficacy, and immunogenicity of Flublok in the prevention of seasonal influenza in adults. Ther Adv Vaccines. 2015;3:97–108.
   PubMedGoogle Scholar
• Ampofo WK, Bachtiar NS, Bakamutumaho B, 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.
   PubMed Web of Science ®Google Scholar
• Robertson JS, Naeve CW, Webster RG, et al. Alternations in the hemagglutinin associated with adaptation of influenza B virus to growth in eggs. Virology. 1985;143:166–174.
   PubMed Web of Science ®Google Scholar
• Katz JM, Naeve CW, Webster RG. Host cell-mediated variation in H3N2 influenza viruses. Virology. 1987;156:386–395.
   PubMed Web of Science ®Google Scholar
• Robertson JS, Bootman JS, Newman R, et al. Structural changes in the hemagglutinin which accompany egg adaptation of an influenza A (H1N1) virus. Virology. 1987;160:31–37.
   PubMed Web of Science ®Google Scholar
• Wang ML, Katz JM, Webster RG. Extensive heterogeneity in the hemagglutinin of egg-grown influenza viruses from different patients. Virology. 1989;171:275–279.
   PubMed Web of Science ®Google Scholar
• Katz JM, Webster RG. Amino acid sequence identity between the HA1 of influenza A (H3N2) viruses grown in mammalian and primary chick kidney cells. J Gen Virol. 1992;73 (Pt 5):1159–1165.
   PubMed Web of Science ®Google Scholar
• Parker L, Wharton SA, Martin SR, et al. Effects of egg-adaptation on receptor-binding and antigenic properties of recent influenza A (H3N2) vaccine viruses. J Gen Virol. 2016;97(6):1333–1344.
   PubMedGoogle Scholar
• Zost SJ, Parkhouse K, Gumina ME, et al. Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains. Proc Natl Acad Sci U S A. 2017;114:12578–12583.
   PubMed Web of Science ®Google Scholar
• Wu NC, Zost SJ, Thompson AJ, et al. A structural explanation for the low effectiveness of the seasonal influenza H3N2 vaccine. PLoS Pathog. 2017;13:e1006682.
   PubMed Web of Science ®Google Scholar
• Manini I, Trombetta CM, Lazzeri G, et al. Egg independent influenza vaccines and vaccine candidates. Vaccines (Basel). 2017;5:18.
   PubMed Web of Science ®Google Scholar
• Rajão DS, Pérez DR. Universal vaccines and vaccine platforms to protect against influenza viruses in humans and agriculture. Front Microbiol. 2018;9:123.
   PubMed Web of Science ®Google Scholar
• Lambert ND, Ovsyannikova IG, Pankratz VS, et al. Understanding the immune response to seasonal influenza vaccination in older adults: a systems biology approach. Expert Rev Vaccines. 2012;11:985–994.
   PubMed Web of Science ®Google Scholar
• Gostic KM, Ambrose M, Worobey M, et al. Potent protection against H5N1 and H7N9 influenza via childhood hemagglutinin imprinting. Science. 2016;354(6313):722–726.
   PubMed Web of Science ®Google Scholar
• Hayward AC, Wang L, Goonetilleke N, et al. Natural T cell-mediated protection against seasonal and pandemic influenza. Results of the Flu Watch cohort study. Am J Respir Crit Care Med. 2015;191(12):1422–1431.
   PubMed Web of Science ®Google Scholar
• Van de Sandt CE, Hillaire ML, Geelhoed-Mieras MM, et al. Human influenza A virus-specific CD8+ T-cell response is long-lived. J Infect Dis. 2015;212(1):81–85.
   PubMed Web of Science ®Google Scholar
• Young B, Zhao X, Cook AR, et al. Do antibody responses to the influenza vaccine persist year-round in the elderly? A systematic review and meta-analysis. Vaccine. 2017;35(2):212–221.
   PubMed Web of Science ®Google Scholar
• Paules CI, Marston HD, Eisinger RW, et al. The pathway to a universal influenza vaccine. Immunity. 2017;47:599–603.
   PubMed Web of Science ®Google Scholar
• Li CK, Rappuoli R, Xu XN. Correlates of protection against influenza infection in humans on the path to a universal vaccine? Curr Opin Immunol. 2013;25(4):470–476.
   PubMed Web of Science ®Google Scholar
• Sui J, Hwang WC, Perez S, et al. Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat Struct Mol Biol. 2009;16(3):265–273.
   PubMed Web of Science ®Google Scholar
• Margine I, Krammer F, Hai R, et al. Hemagglutinin stalk-based universal vaccine constructs protect against group 2 influenza A viruses. J Virol. 2013;87(19):10435–10446.
   PubMed Web of Science ®Google Scholar
• Margine I, Hai R, Albrecht RA, et al. H3N2 influenza virus infection induces broadly reactive hemagglutinin stalk antibodies in humans and mice. J Virol. 2013;87(8):4728–4737.
   PubMed Web of Science ®Google Scholar
• Van der Lubbe JEM, Huizingh J, Verspuij JWA, et al. Mini-hemagglutinin vaccination induces cross-reactive antibodies in pre-exposed NHP that protect mice against lethal influenza challenge. NPJ Vaccines. 2018;3:25.
   PubMed Web of Science ®Google Scholar
• Ermler ME, Kirkpatrick E, Sun W, et al. Chimeric hemagglutinin constructs induce broad protection against influenza b virus challenge in the mouse model. J Virol. 2017;91(12):e00286–17.
   PubMed Web of Science ®Google Scholar
• Holzer B, Morgan SB, Matsuoka Y, et al. Comparison of heterosubtypic protection in ferrets and pigs induced by a single-cycle influenza vaccine. J Immunol. 2018;200(12):4068–4077.
   PubMed Web of Science ®Google Scholar
• Mc Cullough KC, Bassi I, Milona P, et al. Self-replicating replicon-rna delivery to dendritic cells by chitosan-nanoparticles for translation in vitro and in vivo. Mol Ther Nucleic Acids. 2014 Jul;8(3):e173.
   Google Scholar
• Chahal JS, Khan OF, Cooper CL, et al. Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and toxoplasma gondii challenges with a single dose. Proc Natl Acad Sci U S A. 2016 Jul 19;113(29):E4133–E4142. Erratumin: Proc Natl Acad Sci U S A. 2016;113(35):E5250.
   PubMed Web of Science ®Google Scholar
• Vogel AB, Lambert L, Kinnear E, et al. Self-amplifying RNA vaccines give equivalent protection against influenza to mRNA vaccines but at much lower doses. Mol Ther. 2018;26(2):446–455.
   PubMed Web of Science ®Google Scholar
• Wanitchang A, Wongthida P, Jongkaewwattana A. Influenza B virus M2 protein can functionally replace its influenza A virus counterpart in promoting virus replication. Virology. 2016;498:99–108.
   PubMed Web of Science ®Google Scholar
• Lutz J, Lazzaro S, Habbeddine M, et al. Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines. NPJ Vaccines. 2017;2:29.
   PubMed Web of Science ®Google Scholar
• Liang F, Lindgren G, Lin A, et al. Efficient targeting and activation of antigen-presenting cells in vivo after modified mRNA vaccine administration in rhesus macaques. Mol Ther. 2017;25(12):2635–2647.
   PubMed Web of Science ®Google Scholar
• Steel J, Lowen AC, Wang TT, et al. Influenza virus vaccine based on the conserved hemagglutinin stalk domain. MBio. 2010;1(1):pii: e00018–10.
   PubMed Web of Science ®Google Scholar
• Pica N, Hai R, Krammer F, et al. Hemagglutinin stalk antibodies elicited by the 2009 pandemic influenza virus as a mechanism for the extinction of seasonal H1N1 viruses. Proc Natl Acad Sci U S A. 2012;109:2573–2578.
   PubMed Web of Science ®Google Scholar
• Kirchenbaum GA, Carter DM, Ross TM. Sequential infection in ferrets with antigenically distinct seasonal H1N1 influenza viruses boosts hemagglutinin stalk-specific antibodies. J Virol. 2015 Nov 11;90(2):1116–1128.
   PubMed Web of Science ®Google Scholar
• Wei CJ, Boyington JC, McTamney PM, et al. Induction of broadly neutralizing H1N1 influenza antibodies by vaccination. Science. 2010;329(5995):1060–1064.
   PubMed Web of Science ®Google Scholar
• Whittle JR, Wheatley AK, Wu L, et al. Flow cytometry reveals that H5N1 vaccination elicits cross-reactive stem-directed antibodies from multiple Ig heavy-chain lineages. J Virol. 2014;88:4047–4057.
   PubMed Web of Science ®Google Scholar
• Neu KE, Henry Dunand CJ, Wilson PC. Heads, stalks and everything else: how can antibodies eradicate influenza as a human disease? Curr Opin Immunol. 2016;42:48–55.
   PubMed Web of Science ®Google Scholar
• Nachbagauer R, Liu WC, Choi A, et al. A universal influenza virus vaccine candidate confers protection against pandemic H1N1 infection in preclinical ferret studies. NPJ Vaccines. 2017;2:26.
   PubMed Web of Science ®Google Scholar
• Ellebedy AH, Ahmed R. Re-engaging cross-reactive memory B cells: the influenza puzzle. Front Immunol. 2012;3:53.
   PubMed Web of Science ®Google Scholar
• Valkenburg SA, Mallajosyula VV, Li OT, et al. Stalking influenza by vaccination with pre fusion headless HA mini-stem. Sci Rep. 2016;6:22666.
   PubMed Web of Science ®Google Scholar
• Impagliazzo A, Milder F, Kuipers H, et al. A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen. Science. 2015;349(6254):1301–1306.
   PubMed Web of Science ®Google Scholar
• Liu W-C, Jan J-T, Huang Y-J, et al. Unmasking stem-specific neutralizing epitopes by abolishing n-linked glycosylation sites of influenza virus hemagglutinin proteins for vaccine design. J Virol. 2016;90(19):8496–8508.
   PubMed Web of Science ®Google Scholar
• Yassine HM, Boyington JC, McTamney PM, et al. Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection. Nat Med. 2015;21:1065–1070.
   PubMed Web of Science ®Google Scholar
• Sutton TC, Chakraborty S, Mallajosyula VVA, et al. Protective efficacy of influenza group 2 hemagglutinin stem-fragment immunogen vaccines. NPJ Vaccines. 2017;2:35.
   PubMed Web of Science ®Google Scholar
• Rajendran M, Sun W, Comella P, et al. An immuno-assay to quantify influenza virus hemagglutinin with correctly folded stalk domains in vaccine preparations. PLoS One. 2018;13(4):e0194830.
   PubMed Web of Science ®Google Scholar
• Jacobsen H, Rajendran M, Choi A, et al. Influenza virus hemagglutinin stalk-specific antibodies in human serum are a surrogate marker for in vivo protection in a serum transfer mouse challenge model. mBio. 2017;8(5):e01463–17.
   PubMed Web of Science ®Google Scholar
• Pavlova S, D‘Alessio F, Houard S, et al. Immunoassay standardisation for “universal” influenza vaccines. Influenza Other Respir Viruses. 2017;11(3):194–201.
   PubMed Web of Science ®Google Scholar
• Nachbagauer R, Krammer F. Universal influenza virus vaccines and therapeutic antibodies. Clin Microbiol Infect. 2017;23:222–228.
   PubMed Web of Science ®Google Scholar
• Krammer F, Pica N, Hai R, et al. Chimeric hemagglutinin influenza virus vaccine constructs elicit broadly protective stalk-specific antibodies. J Virol. 2013;87:6542–6550.
   PubMed Web of Science ®Google Scholar
• Krammer F, Palese P. Advances in the development of influenza virus vaccines. Nat Rev Drug Discov. 2015;14:167–182.
   PubMed Web of Science ®Google Scholar
• Mancini N, Solforosi L, Clementi N, et al. A potential role for monoclonal antibodies in prophylactic and therapeutic treatment of influenza. Antiviral Res. 2011;92:15–26.
   PubMed Web of Science ®Google Scholar
• Hiroi S, Kuhara M, Kishi Y, et al. Human monoclonal antibodies neutralizing influenza virus A/H1N1pdm09 and seasonal A/H1N1 strains - Distinct Ig gene repertoires with a similar action mechanism. Immunobiology. 2018;223:319–326.
   PubMed Web of Science ®Google Scholar
• Ekiert DC, Kashyap AK, Steel J, et al. Cross-neutralization of influenza A viruses mediated by a single antibody loop. Nature. 2012;489:526–532.
   PubMed Web of Science ®Google Scholar
• Dreyfus C, Laursen NS, Kwaks T, et al. Highly conserved protective epitopes on influenza B viruses. Science. 2012;337:1343–1348.
   PubMed Web of Science ®Google Scholar
• Yoon A, Yi KS, Chang SY, et al. An anti-influenza virus antibody inhibits viral infection by reducing nucleus entry of influenza nucleoprotein. PLoS One. 2015;10:e0141312.
   PubMed Web of Science ®Google Scholar
• Carter DM, Darby CA, Lefoley BC, et al. Design and characterization of a computationally optimized broadly reactive hemagglutinin vaccine for H1N1 influenza viruses. J Virol. 2016;90:4720–4734.
   PubMed Web of Science ®Google Scholar
• Doyle TM, Hashem AM, Li C, et al. Universal anti-neuraminidase antibody inhibiting all influenza A subtypes. Antiviral Res. 2013;100(2):567–574.
   PubMed Web of Science ®Google Scholar
• Eichelberger MC, Wan H. Influenza neuraminidase as a vaccine antigen. Curr Top Microbiol Immunol. 2015;386:275–299.
   PubMed Web of Science ®Google Scholar
• Couch RB, Atmar RL, Franco LM, et al. Antibody correlates and predictors of immunity to naturally occurring influenza in humans and the importance of antibody to the neuraminidase. J Infect Dis. 2013;207:974–981.
   PubMed Web of Science ®Google Scholar
• Couch RB, Kasel JA, Gerin JL, et al. Induction of partial immunity to influenza by a neuraminidase-specific vaccine. J Infect Dis. 1974;129(4):411–420.
   PubMed Web of Science ®Google Scholar
• Murphy BR, Kasel JA, Chanock RM. Association of serum anti-neuraminidase antibody with resistance to influenza in man. N Engl J Med. 1972;286(25):1329–1332.
   PubMed Web of Science ®Google Scholar
• Monto AS, Petrie JG, Cross RT, et al. Antibody to influenza virus neuraminidase: an independent correlate of protection. J Infect Dis. 2015;212(8):1191–1199.
   PubMed Web of Science ®Google Scholar
• Strauch EM, Bernard SM, La D, et al. Computational design of trimeric influenza neutralizing proteins targeting the hemagglutinin receptor binding site. Nat Biotechnol. 2017;35:667–671.
   PubMed Web of Science ®Google Scholar
• Wan H, Gao J, Xu K, et al. Molecular basis for broad neuraminidase immunity: conserved epitopes in seasonal and pandemic H1N1 as well as H5N1 influenza viruses. J Virol. 2013;87(16):9290–9300.
   PubMed Web of Science ®Google Scholar
• Eichelberger MC, Morens DM, Taubenberger JK. Neuraminidase as an influenza vaccine antigen: a low hanging fruit, ready for picking to improve vaccine effectiveness. Curr Opin Immunol. 2018;53:38–44.
   PubMed Web of Science ®Google Scholar
• Fritz R, Sabarth N, Kiermayr S, et al. A vero cell-derived whole-virus H5N1 vaccine effectively induces neuraminidase- inhibiting antibodies. J Infect Dis. 2012;205(28–34):21.
   Google Scholar
• Cate TR, Rayford Y, Nino D, et al. A high dosage influenza vaccine induced significantly more neuraminidase antibody than standard vaccine among elderly subjects. Vaccine. 2010;28:2076–2079.
   PubMed Web of Science ®Google Scholar
• Couzens L, Gao J, Westgeest K, et al. An optimized enzyme-linked lectin assay to measure influenza A virus neuraminidase inhibition antibody titers in human sera. J Virol Methods. 2014;210:7–14.
   PubMed Web of Science ®Google Scholar
• Eichelberger MC, Couzens L, Gao Y, et al. Comparability of neuraminidase inhibition antibody titers measured by enzyme-linked lectin assay (ELLA) for the analysis of influenza vaccine immunogenicity. Vaccine. 2016;34(4):458–465.
   PubMed Web of Science ®Google Scholar
• El Bakkouri K, Descamps F, De Filette M, et al. Universal vaccine based on ectodomain of matrix protein 2 of influenza A: Fc receptors and alveolar macrophages mediate protection. J Immunol. 2011;186:1022–1031.
   PubMed Web of Science ®Google Scholar
• Neirynck S, Deroo T, Saelens X, et al. A universal influenza A vaccine based on the extracellular domain of the M2 protein. Nat Med. 1999;5:1157–1163.
   PubMed Web of Science ®Google Scholar
• Schotsaert M, De Filette M, Fiers W, et al. Universal M2 ectodomain-based influenza A vaccines: preclinical and clinical developments. Expert Rev Vaccines. 2009;8:499–508.
   PubMed Web of Science ®Google Scholar
• Kim MC, Song JM, Eunju O, et al. Virus-like particles containing multiple M2 extracellular domains confer improved cross-protection against various subtypes of influenza virus. Mol Ther. 2013;21:485–492.
   PubMed Web of Science ®Google Scholar
• Turley CB, Rupp RE, Johnson C, et al. Safety and immunogenicity of a recombinant M2e flagellin influenza vaccine (STF2.4xM2e) in healthy adults. Vaccine. 2011;29:5145–5152.
   PubMed Web of Science ®Google Scholar
• Kolpe A, Schepens B, Fiers W, et al. M2-based influenza vaccines: recent advances and clinical potential. Expert Rev Vaccines. 2017;16:123–136.
   PubMed Web of Science ®Google Scholar
• Kim EH, Han GY, Nguyen H. An adenovirus-vectored influenza vaccine induces durable cross-protective hemagglutinin stalk antibody responses in mice. Viruses. 2017 Aug 21;9(8):pii: E234.
   Web of Science ®Google Scholar
• Soboleski MR, Gabbard JD, Price GE, et al. Cold-adapted influenza and recombinant adenovirus vaccines induce cross-protective immunity against pH1N1 challenge in mice. PLoS One. 2011;6(7):e21937.
   PubMed Web of Science ®Google Scholar
• López-Sagaseta J, Malito E, Rappuoli R, et al. Self-assembling protein nanoparticles in the design of vaccines. Comput Struct Biotechnol J. 2016;14:58–68.
   PubMed Web of Science ®Google Scholar
• Feshchenko E, Rhodes DG, Felberbaum R, et al. Pandemic influenza vaccine: characterization of A/California/07/2009 (H1N1) recombinant hemagglutinin protein and insights into H1N1 antigen stability. BMC Biotechnol. 2012;12:77.
   PubMed Web of Science ®Google Scholar
• Mosafer J, Badiee A, Mohammadamini Z, et al. Immunization against PR8 influenza virus with chitosan-coated ISCOMATRIX nanoparticles. Artif Cells Nanomed Biotechnol. 2018;46(sup2):587-593.
   Web of Science ®Google Scholar
• Yap KL, Ada GL. The recovery of mice from influenza A virus infection: adoptive transfer of immunity with influenza virus-specific cytotoxic T lymphocytes recognizing a common virion antigen. Scand J Immunol. 1978;8(5):413–420.
   PubMed Web of Science ®Google Scholar
• Flynn KJ, Belz GT, Altman JD, et al. Virus-specific CD8+ T cells in primary and secondary influenza pneumonia. Immunity. 1998;8(6):683–691.
   PubMed Web of Science ®Google Scholar
• Kumar A, Meldgaard TS, Bertholet S. Novel platforms for the development of a universal influenza vaccine. Front Immunol. 2018;9:600.
   PubMed Web of Science ®Google Scholar
• Duvvuri VR, Moghadas SM, Guo H, et al. Highly conserved cross-reactive CD4+ T-cell HA-epitopes of seasonal and the 2009 pandemic influenza viruses. Influenza Other Respir Viruses. 2010;4(5):249–258.
   PubMed Web of Science ®Google Scholar
• Sridhar S, Begom S, Bermingham A, et al. Cellular immune correlates of protection against symptomatic pandemic influenza. Nat Med. 2013;19(10):1305–1312.
   PubMed Web of Science ®Google Scholar
• Steinhoff MC, Fries LF, Karron RA, et al. Effect of heterosubtypic immunity on infection with attenuated influenza A virus vaccines in young children. J Clin Microbiol. 1993;31(4):836–838.
   PubMed Web of Science ®Google Scholar
• Belshe R, Lee MS, Walker RE, et al. Safety, immunogenicity and efficacy of intranasal, live attenuated influenza vaccine. Expert Rev Vaccines. 2004;3(6):643–654.
   PubMedGoogle Scholar
• Nogales A, Baker SF, Domm W, et al. Development and applications of single-cycle infectious influenza A virus (sciIAV). Virus Res. 2016;216:26–40.
   PubMed Web of Science ®Google Scholar
• Si L, Xu H, Zhou X, et al. Generation of influenza A viruses as live but replication-incompetent virus vaccines. Science. 2016;354(6316):1170–1173.
   PubMed Web of Science ®Google Scholar
• Broadbent AJ, Santos CP, Anafu A, et al. Evaluation of the attenuation, immunogenicity, and efficacy of a live virus vaccine generated by codon-pair bias de-optimization of the 2009 pandemic H1N1 influenza virus, in ferrets. Vaccine. 2016;34(4):563–570.
   PubMed Web of Science ®Google Scholar
• Cox A, Baker SF, Nogales A, et al. Development of a mouse-adapted live attenuated influenza virus that permits in vivo analysis of enhancements to the safety of live attenuated influenza virus vaccine. J Virol. 2015;89(6):3421–3426.
   PubMed Web of Science ®Google Scholar
• Morgan SB, Hemmink JD, Porter E, et al. Aerosol delivery of a candidate universal influenza vaccine reduces viral load in pigs challenged with pandemic H1N1 virus. J Immunol. 2016;196(12):5014–5023.
   PubMed Web of Science ®Google Scholar
• Lillie PJ, Berthoud TK, Powell TJ, 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.
   PubMed Web of Science ®Google Scholar
• Tully CM, Chinnakannan S, Mullarkey CE, et al. Novel bivalent viral-vectored vaccines induce potent humoral and cellular immune responses conferring protection against stringent influenza A virus challenge. J Immunol. 2017 Jul 19;199(4):1333–1341.
   PubMed Web of Science ®Google Scholar
• Antrobus RD, Berthoud TK, Mullarkey CE, et al. Coadministration of seasonal influenza vaccine and MVA-NP+M1 simultaneously achieves potent humoral and cell-mediated responses. Mol Ther. 2014;22(1):233–238.
   PubMed Web of Science ®Google Scholar
• Fries LF, Smith GE, Glenn GM. A recombinant viruslike particle influenza A (H7N9) vaccine. N Engl J Med. 2013 Dec 26;369(26):2564–2566.
   PubMed Web of Science ®Google Scholar
• Magnusson SE, Altenburg AF, Bengtsson KL, et al. Matrix-M™ adjuvant enhances immunogenicity of both protein- and modified vaccinia virus Ankara-based influenza vaccines in mice. Immunol Res. 2018;66(2):224–233.
   PubMed Web of Science ®Google Scholar
• Antrobus RD, Coughlan L, Berthoud TK, et al. Clinical assessment of a novel recombinant simian adenovirus ChAdOx1 as a vectored vaccine expressing conserved influenza A antigens. Mol Ther. 2014;22(3):668–674.
   PubMed Web of Science ®Google Scholar
• Florek NW, Weinfurter JT, Jegaskanda S, et al. Modified vaccinia virus Ankara encoding influenza virus hemagglutinin induces heterosubtypic immunity in macaques. J Virol. 2014;88(22):13418–13428.
   PubMed Web of Science ®Google Scholar
• Florek NW, Kamlangdee A, Mutschler JP, et al. A modified vaccinia Ankara vaccine vector expressing a mosaic H5 hemagglutinin reduces viral shedding in rhesus macaques. PLoS One. 2017;12(8):e0181738.
   PubMed Web of Science ®Google Scholar
• Pleguezuelos O, Robinson S, Stoloff GA, et al. Synthetic influenza vaccine (FLU-v) stimulates cell mediated immunity in a double-blind, randomised, placebo-controlled phase I trial. Vaccine. 2012;30:4655–4660.
   PubMed Web of Science ®Google Scholar
• Atsmon J, Caraco Y, Ziv-Sefer S, et al. Priming by a novel universal influenza vaccine (Multimeric-001)-a gateway for improving immune response in the elderly population. Vaccine. 2014;32(44):5816–5823.
   PubMed Web of Science ®Google Scholar
• Petsch B, Schnee M, Vogel AB, et al. Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Nat Biotechnol. 2012;30(12):1210–1216.
   PubMed Web of Science ®Google Scholar
• Hekele A, Bertholet S, Archer J, et al. Rapidly produced SAM(®) vaccine against H7N9 influenza is immunogenic in mice. Emerg Microbes Infect. 2013;2(8):e52.
   PubMed Web of Science ®Google Scholar
• Magini D, Giovani C, Mangiavacchi S, et al. Self-amplifying mRNA vaccines expressing multiple conserved influenza antigens confer protection against homologous and heterosubtypic viral challenge. PLoS One. 2016;11(8):e0161193.
   PubMed Web of Science ®Google Scholar
• Brazzoli M, Magini D, Bonci A, et al. Induction of broad-based immunity and protective efficacy by self-amplifying mRNA vaccines encoding influenza virus hemagglutinin. J Virol. 2016;90(1):332–344.
   PubMed Web of Science ®Google Scholar
• Bahl K, Senn JJ, Yuzhakov O, et al. Preclinical and clinical demonstration of immunogenicity by mRNA vaccines against H10N8 and H7N9 influenza viruses. Mol Ther. 2017;25(6):1316–1327.
   PubMed Web of Science ®Google Scholar
• Valkenburg SA, Leung NHL, Bull MB, et al. The hurdles from bench to bedside in the realization and implementation of a universal influenza vaccine. Front Immunol. 2018;9:1479.
   PubMed Web of Science ®Google Scholar
• WHO preferred product characteristics for next-generation influenza vaccines [Internet]. WHO; [cited 2018 Feb 11]. Available from: http://www.who.int/immunization/documents/ISBN_978-92-4-151246-6/en
   Google Scholar
• Potter CW, Oxford JS. Determinants of immunity to influenza infection in man. Br Med Bull. 1979;35(1):69–75.
   PubMed Web of Science ®Google Scholar
• Hobson D, Curry RL, Beare AS, et al. The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses. J Hyg. 1972;70(4):767–777.
   PubMedGoogle Scholar
• Reber A, Katz J. Immunological assessment of influenza vaccines and immune correlates of protection. Expert Rev Vaccines. 2013;12(5):519–536.
   PubMed Web of Science ®Google Scholar
• European medicines agency. Guidelines on influenza vaccines; [cited 2018 Feb 11]. Available from: https://www.ema.europa.eu/documents/scientific-guideline/influenza-vaccines-non-clinical-clinical-module_en.pdf
   Google Scholar
• Meiklejohn G, Kempe CH, Thalman WG, et al. Evaluation of monovalent influenza vaccines. II. Observations during an influenza a-prime epidemic. Am J Hyg. 1952;55(1):12–21.
   PubMed Web of Science ®Google Scholar