The evolution of seasonal influenza viruses (original) (raw)

• Stöhr, K. Influenza—WHO cares. Lancet Infect. Dis. 2, 517 (2002).
  PubMed Google Scholar
• Zambon, M. C. Epidemiology and pathogenesis of influenza. J. Antimicrob. Chemother. 44, 3–9 (1999).
  CAS PubMed Google Scholar
• Russell, C. A. et al. Improving pandemic influenza risk assessment. eLife 3, e03883 (2014).
  PubMed PubMed Central Google Scholar
• Tong, S. et al. New World bats harbor diverse influenza A viruses. PLoS Pathog. 9, e1003657 (2013).
  PubMed PubMed Central Google Scholar
• Francis, T. A. New type of virus from epidemic influenza. Science 92, 405–408 (1940).
  PubMed Google Scholar
• Biere, B., Bauer, B. & Schweiger, B. Differentiation of influenza B virus lineages Yamagata & Victoria by real-time PCR. J. Clin. Microbiol. 48, 1425–1427 (2010).
  PubMed PubMed Central Google Scholar
• Kanegae, Y. et al. Evolutionary pattern of the hemagglutinin gene of influenza B viruses isolated in Japan: cocirculating lineages in the same epidemic season. J. Virol. 64, 2860–2865 (1990).
  CAS PubMed PubMed Central Google Scholar
• Chen, W. et al. A novel influenza A virus mitochondrial protein that induces cell death. Nat. Med. 7, 1306–1312 (2001).
  CAS PubMed Google Scholar
• Jagger, B. W. et al. An overlapping protein-coding region in influenza A virus segment 3 modulates the host response. Science 337, 199–204 (2012).
  CAS PubMed PubMed Central Google Scholar
• Cohen, M. et al. Influenza A penetrates host mucus by cleaving sialic acids with neuraminidase. Virol. J. 10, 321 (2013).
  PubMed PubMed Central Google Scholar
• Westgeest, K. B. et al. Genomewide analysis of reassortment and evolution of human influenza A(H3N2) viruses circulating between 1968 and 2011. J. Virol. 88, 2844–2857 (2014).
  PubMed PubMed Central Google Scholar
• Smith, D. J. et al. Mapping the antigenic and genetic evolution of influenza virus. Science 305, 371–376 (2004). This is a seminal study that documented the continuous genetic but punctuated antigenic evolution of A/H3N2 viruses and introduced antigenic cartography — a computational tool for quantifying differences in virus antigenic phenotype.
  CAS PubMed Google Scholar
• Westgeest, K. B. et al. Genetic evolution of the neuraminidase of influenza A (H3N2) viruses from 1968 to 2009 and its correspondence to haemagglutinin evolution. J. Gen. Virol. 93, 1996–2007 (2012).
  CAS PubMed PubMed Central Google Scholar
• Sandbulte, M. R. et al. Discordant antigenic drift of neuraminidase and hemagglutinin in H1N1 and H3N2 influenza viruses. Proc. Natl Acad. Sci. USA 108, 20748–20753 (2011).
  CAS PubMed Google Scholar
• Salk, J. E. & Suriano, P. C. Importance of antigenic composition of influenza virus vaccine in protecting against the natural disease. Am. J. Publ. Health Nat. Health 39, 345–355 (1949).
  CAS Google Scholar
• Kilbourne, E. D. et al. The total influenza vaccine failure of 1947 revisited: major intrasubtypic antigenic change can explain failure of vaccine in a post-World War II epidemic. Proc. Natl Acad. Sci. USA 99, 10748–10752 (2002).
  CAS PubMed Google Scholar
• Tricco, A. C. et al. Comparing influenza vaccine efficacy against mismatched and matched strains: a systematic review and meta-analysis. BMC Med. 11, 153 (2013).
  PubMed PubMed Central Google Scholar
• Linderman, S. L. et al. Potential antigenic explanation for atypical H1N1 infections among middle-aged adults during the 2013–2014 influenza season. Proc Natl Acad. Sci. USA 111, 15798–15803 (2014).
  CAS PubMed Google Scholar
• Cobey, S. & Hensley, S. E. Immune history and influenza virus susceptibility. Curr. Opin. Virol. 22, 105–111 (2017).
  CAS PubMed PubMed Central Google Scholar
• DiLillo, D. J., Palese, P., Wilson, P. C. & Ravetch, J. V. Broadly neutralizing anti-influenza antibodies require Fc receptor engagement for in vivo protection. J. Clin. Invest. 126, 605–610 (2016).
  PubMed PubMed Central Google Scholar
• Terajima, M. et al. Complement-dependent lysis of influenza A virus-infected cells by broadly cross-reactive human monoclonal antibodies. J. Virol. 85, 13463–13467 (2011).
  CAS PubMed PubMed Central Google Scholar
• Jegaskanda, S., Weinfurter, J. T., Friedrich, T. C. & Kent, S. J. Antibody-dependent cellular cytotoxicity is associated with control of pandemic H1N1 influenza virus infection of macaques. J. Virol. 87, 5512–5522 (2013).
  CAS PubMed PubMed Central Google Scholar
• Chen, R. & Holmes, E. C. The evolutionary dynamics of human influenza B virus. J. Mol. Evol. 66, 655–663 (2008).
  CAS PubMed PubMed Central Google Scholar
• Bedford, T. et al. Global circulation patterns of seasonal influenza viruses vary with antigenic drift. Nature 523, 217–220 (2015). This is the first detailed comparison of the global circulation dynamics of all four seasonal influenza viruses and is the most complete characterization of the global dynamics of seasonal influenza viruses to date.
  CAS PubMed PubMed Central Google Scholar
• Vijaykrishna, D. et al. The contrasting phylodynamics of human influenza B viruses. eLife 4, e05055 (2015).
  PubMed PubMed Central Google Scholar
• Kucharski, A. J. et al. Estimating the life course of influenza A(H3N2) antibody responses from cross-sectional data. PLoS Biol. 13, e1002082 (2015).
  PubMed PubMed Central Google Scholar
• Fonville, J. M. et al. Antibody landscapes after influenza virus infection or vaccination. Science 346, 996–1000 (2014).
  CAS PubMed PubMed Central Google Scholar
• Cheung, P. P. H. et al. Generation and characterization of influenza A viruses with altered polymerase fidelity. Nat. Commun. 5, 4794 (2014).
  CAS PubMed PubMed Central Google Scholar
• Virelizier, J.-L. Host defenses against influenza virus: the role of anti-hemagglutinin antibody. J. Immunol. 115, 434–439 (1975).
  CAS PubMed Google Scholar
• Bizebard, T. et al. Structure of influenza virus haemagglutinin complexed with a neutralizing antibody. Nature 376, 92–94 (1995).
  CAS PubMed Google Scholar
• Margine, I. et al. H3N2 influenza virus infection induces broadly reactive hemagglutinin stalk antibodies in humans and mice. J. Virol. 87, 4728–4737 (2013).
  CAS PubMed PubMed Central Google Scholar
• Moody, M. A. et al. H3N2 influenza infection elicits more cross-reactive and less clonally expanded anti-hemagglutinin antibodies than influenza vaccination. PLoS ONE 6, e25797 (2011).
  CAS PubMed PubMed Central Google Scholar
• Nachbagauer, R. et al. Age dependence and isotype specificity of influenza virus hemagglutinin stalk-reactive antibodies in humans. mBio 7, e01996-15 (2016). This is a detailed analysis of how broadly influenza neutralizing antibodies accumulate with age and of their possible role in the decreased rate of influenza infection among elderly individuals.
  PubMed PubMed Central Google Scholar
• Wiley, D. C., Wilson, I. A. & Skehel, J. J. Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature 289, 373–378 (1981).
  CAS PubMed Google Scholar
• Skehel, J. J. et al. A carbohydrate side chain on hemagglutinins of Hong Kong influenza viruses inhibits recognition by a monoclonal antibody. Proc. Natl Acad. Sci. USA 81, 1779–1783 (1984).
  CAS PubMed Google Scholar
• Gerhard, W., Yewdell, J., Frankel, M. E. & Webster, R. Antigenic structure of influenza virus haemagglutinin defined by hybridoma antibodies. Nature 290, 713–717 (1981).
  CAS PubMed Google Scholar
• Koel, B. F. et al. Substitutions near the receptor binding site determine major antigenic change during influenza virus evolution. Science 342, 976–979 (2013). This is a key paper showing that the majority of substantial antigenic changes as determined by experimental assays from 1968 to – have been associated with amino acid substitutions in just seven positions in the HA protein.
  CAS PubMed Google Scholar
• Barr, I. G. et al. WHO recommendations for the viruses used in the 2013–2014 Northern Hemisphere influenza vaccine: epidemiology, antigenic and genetic characteristics of influenza A(H1N1)pdm09, A(H3N2) and B influenza viruses collected from October 2012 to January 2013. Vaccine 32, 4713–4725 (2014).
  PubMed Google Scholar
• Klimov, A. I. et al. WHO recommendations for the viruses to be used in the 2012 Southern Hemisphere influenza vaccine: epidemiology, antigenic and genetic characteristics of influenza A(H1N1)pdm09, A(H3N2) and B influenza viruses collected from February to September 2011. Vaccine 30, 6461–6471 (2012).
  PubMed Google Scholar
• Koel, B. F. et al. Antigenic variation of clade 2.1 H5N1 virus is determined by a few amino acid substitutions immediately adjacent to the receptor binding site. mBio 5, e01070-14 (2014).
  PubMed PubMed Central Google Scholar
• Abente, E. J. et al. The molecular determinants of antibody recognition and antigenic drift in the H3 hemagglutinin of swine influenza A virus. J. Virol. 90, 8266–8280 (2016).
  CAS PubMed PubMed Central Google Scholar
• Lewis, N. S. et al. The global antigenic diversity of swine influenza A viruses. eLife 5, e12217 (2016).
  PubMed PubMed Central Google Scholar
• Lewis, N. S. et al. Antigenic and genetic evolution of equine influenza A (H3N8) virus from 1968 to 2007. J. Virol. 85, 12742–12749 (2011).
  CAS PubMed PubMed Central Google Scholar
• Doud, M. B., Hensley, S. E. & Bloom, J. D. Complete mapping of viral escape from neutralizing antibodies. PLoS Pathog. 13, e1006271 (2017). This study demonstrates the excellent use of tools for deep mutational scanning to investigate the virus genetic consequences of antibody selection.
  PubMed PubMed Central Google Scholar
• Kirchenbaum, G. A., Carter, D. M. & Ross, T. M. Sequential infection in ferrets with antigenically distinct seasonal H1N1 influenza viruses boosts hemagglutinin stalk-specific antibodies. J. Virol. 90, 1116–1128 (2016).
  CAS PubMed Google Scholar
• Nachbagauer, R. et al. Induction of broadly reactive anti-hemagglutinin stalk antibodies by an H5N1 vaccine in humans. J. Virol. 88, 13260–13268 (2014).
  PubMed PubMed Central Google Scholar
• Okuno, Y., Isegawa, Y., Sasao, F. & Ueda, S. A common neutralizing epitope conserved between the hemagglutinins of influenza A virus H1 and H2 strains. J. Virol. 67, 2552–2558 (1993).
  CAS PubMed PubMed Central Google Scholar
• Chai, N. et al. Two escape mechanisms of influenza A Virus to a broadly neutralizing stalk-binding antibody. PLoS Pathog. 12, e1005702 (2016). This study provides an important functional demonstration of the ability of influenza viruses to escape broadly neutralizing antibodies through a small number of amino acid substitutions.
  PubMed PubMed Central Google Scholar
• Schulman, J. L., Khakpour, M. & Kilbourne, E. D. Protective effects of specific immunity to viral neuraminidase on influenza virus infection of mice. J. Virol. 2, 778–786 (1968).
  CAS PubMed PubMed Central Google Scholar
• Murphy, B. R., Kasel, J. A. & Chanock, R. M. Association of serum anti-neuraminidase antibody with resistance to influenza in man. N. Engl. J. Med. 286, 1329–1332 (1972).
  CAS PubMed Google Scholar
• Eichelberger, M. C. & Wan, H. Influenza neuraminidase as a vaccine antigen. Curr. Top. Microbiol. Immunol. 386, 275–299 (2015).
  CAS PubMed Google Scholar
• Sultana, I. et al. Stability of neuraminidase in inactivated influenza vaccines. Vaccine 32, 2225–2230 (2014).
  CAS PubMed Google Scholar
• Koelle, K., Cobey, S., Grenfell, B. & Pascual, M. Epochal evolution shapes the phylodynamics of interpandemic influenza A (H3N2) in humans. Science 314, 1898–1903 (2006).
  CAS PubMed Google Scholar
• Koelle, K. & Rasmussen, D. A. The effects of a deleterious mutation load on patterns of influenza A/H3N2's antigenic evolution in humans. eLife 4, e07361 (2015).
  PubMed PubMed Central Google Scholar
• Zinder, D., Bedford, T., Gupta, S. & Pascual, M. The roles of competition and mutation in shaping antigenic and genetic diversity in influenza. PLoS Pathog. 9, e1003104 (2013).
  CAS PubMed PubMed Central Google Scholar
• Recker, M., Pybus, O. G., Nee, S. & Gupta, S. The generation of influenza outbreaks by a network of host immune responses against a limited set of antigenic types. Proc. Natl Acad. Sci. USA 104, 7711–7716 (2007).
  CAS PubMed Google Scholar
• Meyer, A. G. & Wilke, C. O. Geometric constraints dominate the antigenic evolution of influenza H3N2 hemagglutinin. PLoS Pathog. 11, e1004940 (2015).
  PubMed PubMed Central Google Scholar
• Bedford, T., Rambaut, A. & Pascual, M. Canalization of the evolutionary trajectory of the human influenza virus. BMC Biol. 10, 38 (2012).
  PubMed PubMed Central Google Scholar
• Gog, J. R. The impact of evolutionary constraints on influenza dynamics. Vaccine 26, C15–C24 (2008).
  PubMed Google Scholar
• Andreasen, V. & Sasaki, A. Shaping the phylogenetic tree of influenza by cross-immunity. Theor. Popul. Biol. 70, 164–173 (2006).
  PubMed Google Scholar
• Hensley, S. E. et al. Hemagglutinin receptor binding avidity drives influenza A virus antigenic drift. Science 326, 734–736 (2009).
  CAS PubMed PubMed Central Google Scholar
• Gong, L. I. & Bloom, J. D. Epistatically interacting substitutions are enriched during adaptive protein evolution. PLoS Genet. 10, e1004328 (2014). The study is a key example of how the specific genetic context in which mutations occur can have substantial effect on the resulting fitness of viruses.
  PubMed PubMed Central Google Scholar
• Bloom, J. D., Gong, L. I. & Baltimore, D. Permissive secondary mutations enable the evolution of influenza oseltamivir resistance. Science 328, 1272–1275 (2010).
  CAS PubMed PubMed Central Google Scholar
• Leonard, A. S. et al. Deep sequencing of influenza A virus from a human challenge study reveals a selective bottleneck and only limited intrahost genetic diversification. J. Virol. 90, 11247–11258 (2016).
  CAS Google Scholar
• Debbink, K. et al. Vaccination has minimal impact on the intrahost diversity of H3N2 influenza viruses. PLoS Pathog. 13, e1006194 (2017). This study provides an interesting analysis of human virus samples relating within-host virus data to vaccination status and finds a minimal role for vaccine-induced immunity as a source of evolutionary selection pressure.
  PubMed PubMed Central Google Scholar
• McCrone, J. T. et al. The evolutionary dynamics of influenza A virus within and between human hosts. bioRxiv http://dx.doi.org/10.1101/176362 (2017).
• Xue, K. S. et al. Parallel evolution of influenza across multiple spatiotemporal scales. eLife 6, e26875 (2017).
  PubMed PubMed Central Google Scholar
• Parvin, J. D., Moscona, A., Pan, W. T., Leider, J. M. & Palese, P. Measurement of the mutation rates of animal viruses: influenza A virus and poliovirus type 1. J. Virol. 59, 377–383 (1986).
  CAS PubMed PubMed Central Google Scholar
• Nobusawa, E. & Sato, K. Comparison of the mutation rates of human influenza A and B viruses. J. Virol. 80, 3675–3678 (2006).
  CAS PubMed PubMed Central Google Scholar
• Bloom, J. D. An experimentally determined evolutionary model dramatically improves phylogenetic fit. Mol. Biol. Evol. 31, 1956–1978 (2014).
  CAS PubMed PubMed Central Google Scholar
• Pauly, M. D., Procario, M. C. & Lauring, A. S. A novel twelve class fluctuation test reveals higher than expected mutation rates for influenza A viruses. eLife 6, e26437 (2017).
  PubMed PubMed Central Google Scholar
• Sidorenko, Y. & Reichl, U. Structured model of influenza virus replication in MDCK cells. Biotechnol. Bioeng. 88, 1–14 (2004).
  CAS PubMed Google Scholar
• Wu, N.-H. et al. The differentiated airway epithelium infected by influenza viruses maintains the barrier function despite a dramatic loss of ciliated cells. Sci. Rep. 6, 39668 (2016).
  CAS PubMed PubMed Central Google Scholar
• Guillot, L. et al. Involvement of toll-like receptor 3 in the immune response of lung epithelial cells to double-stranded RNA and influenza A virus. J. Biol. Chem. 280, 5571–5580 (2005).
  CAS PubMed Google Scholar
• Alexopoulou, L., Holt, A. C., Medzhitov, R. & Flavell, R. A. Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3. Nature 413, 732–738 (2001).
  CAS PubMed Google Scholar
• Marois, I., Cloutier, A., Garneau, E. & Richter, M. V. Initial infectious dose dictates the innate, adaptive, and memory responses to influenza in the respiratory tract. J. Leukoc. Biol. 92, 107–121 (2012).
  CAS PubMed Google Scholar
• Le Goffic, R. et al. Influenza A virus protein PB1-F2 exacerbates IFN-β expression of human respiratory epithelial cells. J. Immunol. 185, 4812–4823 (2010).
  CAS PubMed Google Scholar
• Le Goffic, R. et al. Transcriptomic analysis of host immune and cell death responses associated with the influenza A virus PB1-F2 protein. PLoS Pathog. 7, e1002202 (2011).
  CAS PubMed PubMed Central Google Scholar
• Everitt, A. R. et al. IFITM3 restricts the morbidity and mortality associated with influenza. Nature 484, 519–523 (2012).
  CAS PubMed PubMed Central Google Scholar
• Zimmermann, P., Manz, B., Haller, O., Schwemmle, M. & Kochs, G. The viral nucleoprotein determines Mx sensitivity of influenza A viruses. J. Virol. 85, 8133–8140 (2011).
  CAS PubMed PubMed Central Google Scholar
• Gnirss, K. et al. Tetherin sensitivity of influenza A viruses is strain specific: role of hemagglutinin and neuraminidase. J. Virol. 89, 9178–9188 (2015).
  CAS PubMed PubMed Central Google Scholar
• Andrews, S. F. et al. Immune history profoundly affects broadly protective B cell responses to influenza. Sci. Transl Med. 7, 316ra192 (2015).
  PubMed PubMed Central Google Scholar
• Slütter, B. et al. Dynamics of influenza-induced lung-resident memory T cells underlie waning heterosubtypic immunity. Sci. Immunol. 2, eaag2031 (2017).
  PubMed PubMed Central Google Scholar
• Baccam, P., Beauchemin, C., Macken, C. A., Hayden, F. G. & Perelson, A. S. Kinetics of influenza A virus infection in humans. J. Virol. 80, 7590–7599 (2006).
  CAS PubMed PubMed Central Google Scholar
• Kitphati, R. et al. Kinetics and longevity of antibody response to influenza A H5N1 virus infection in humans. Clin. Vaccine Immunol. 16, 978–981 (2009).
  CAS PubMed PubMed Central Google Scholar
• Ochsenbein, A. F. et al. Protective long-term antibody memory by antigen-driven and T help-dependent differentiation of long-lived memory B cells to short-lived plasma cells independent of secondary lymphoid organs. Proc. Natl Acad. Sci. USA 97, 13263–13268 (2000).
  CAS PubMed Google Scholar
• Neuzil, K. M. et al. Immunogenicity and reactogenicity of 1 versus 2 doses of trivalent inactivated influenza vaccine in vaccine-naive 5–8-year-old children. J. Infect. Dis. 194, 1032–1039 (2006).
  CAS PubMed Google Scholar
• Renegar, K. B., Small, P. A., Boykins, L. G. & Wright, P. F. Role of IgA versus IgG in the control of influenza viral infection in the murine respiratory tract. J. Immunol. 173, 1978–1986 (2004).
  CAS PubMed Google Scholar
• Stokes, C. R., Soothill, J. F. & Turner, M. W. Immune exclusion is a function of IgA. Nature 255, 745–746 (1975).
  CAS PubMed Google Scholar
• Nachbagauer, R. & Krammer, F. Universal influenza virus vaccines and therapeutic antibodies. Clin Microbiol. Infect. 23, 222–228 (2017).
  CAS PubMed PubMed Central Google Scholar
• Wrammert, J. et al. Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection. J. Exp. Med. 208, 181–193 (2011).
  CAS PubMed PubMed Central Google Scholar
• Davenport, F. M., Hennessy, A. V. & Francis, T. Epidemiologic and immunologic significance of age distribution of antibody to antigenic variants of influenza virus. J. Exp. Med. 98, 641–656 (1953).
  CAS PubMed PubMed Central Google Scholar
• Davenport, F. M., Hennessy, A. V., Stuart-Harris, C. H. & Francis, T. Epidemiology of influenza; comparative serological observations in England and the United States. Lancet 269, 469–474 (1955).
  CAS PubMed Google Scholar
• Miller, M. S. et al. Neutralizing antibodies against previously encountered influenza virus strains increase over time: a longitudinal analysis. Sci Transl Med 5, 198ra107 (2013).
  PubMed PubMed Central Google Scholar
• Lessler, J. et al. Evidence for antigenic seniority in influenza A (H3N2) antibody responses in southern China. PLoS Pathog. 8, e1002802 (2012).
  CAS PubMed PubMed Central Google Scholar
• Davenport, F. M. & Hennessy, A. V. A serologic recapitulation of past experiences with influenza A; antibody response to monovalent vaccine. J. Exp. Med. 104, 85–97 (1956).
  CAS PubMed PubMed Central Google Scholar
• Hobson, D., Curry, R. L., Beare, A. S. & Ward-Gardner, A. The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses. J. Hyg. 70, 767–777 (1972).
  CAS PubMed Google Scholar
• Swayne, D. E. et al. Antibody titer has positive predictive value for vaccine protection against challenge with natural antigenic-drift variants of H5N1 high-pathogenicity avian influenza viruses from Indonesia. J. Virol. 89, 3746–3762 (2015).
  CAS PubMed PubMed Central Google Scholar
• Fox, A. et al. Hemagglutination inhibiting antibodies and protection against seasonal and pandemic influenza infection. J. Infect. 70, 187–196 (2015).
  PubMed PubMed Central Google Scholar
• Ohmit, S. E., Petrie, J. G., Cross, R. T., Johnson, E. & Monto, A. S. Influenza hemagglutination-inhibition antibody titer as a correlate of vaccine-induced protection. J. Infect. Dis. 204, 1879–1885 (2011).
  CAS PubMed Google Scholar
• Hensley, S. E. Challenges of selecting seasonal influenza vaccine strains for humans with diverse pre-exposure histories. Curr. Opin. Virol. 8, 85–89 (2014).
  CAS PubMed Google Scholar
• Frise, R. et al. Contact transmission of influenza virus between ferrets imposes a looser bottleneck than respiratory droplet transmission allowing propagation of antiviral resistance. Sci. Rep. 6, 29793 (2016).
  CAS PubMed PubMed Central Google Scholar
• Varble, A. et al. Influenza A virus transmission bottlenecks are defined by infection route and recipient host. Cell Host Microbe 16, 691–700 (2014). This is an elegant experimental paper showing how route of transmission is an important factor in virus population bottleneck size.
  CAS PubMed PubMed Central Google Scholar
• Moncla, L. H. et al. Selective bottlenecks shape evolutionary pathways taken during mammalian adaptation of a 1918-like avian influenza virus. Cell Host Microbe 19, 169–180 (2016).
  CAS PubMed PubMed Central Google Scholar
• Poon, L. L. M. et al. Quantifying influenza virus diversity and transmission in humans. Nat. Genet. 48, 195–200 (2016).
  CAS PubMed PubMed Central Google Scholar
• Tamerius, J. D. et al. Environmental predictors of seasonal influenza epidemics across temperate and tropical climates. PLoS Pathog. 9, e1003194 (2013).
  CAS PubMed PubMed Central Google Scholar
• Viboud, C., Alonso, W. J. & Simonsen, L. Influenza in tropical regions. PLoS Med. 3, e89 (2006).
  PubMed PubMed Central Google Scholar
• Hirve, S. et al. Influenza seasonality in the tropics and subtropics — when to vaccinate? PLoS ONE 11, e0153003 (2016).
  PubMed PubMed Central Google Scholar
• Lowen, A. C., Mubareka, S., Steel, J. & Palese, P. Influenza virus transmission is dependent on relative humidity and temperature. PLoS Pathog. 3, e151 (2007).
  PubMed Central Google Scholar
• Deyle, E. R., Maher, M. C., Hernandez, R. D., Basu, S. & Sugihara, G. Global environmental drivers of influenza. Proc. Natl Acad. Sci. USA 113, 13081–13086 (2016).
  CAS PubMed Google Scholar
• Shaman, J. & Kohn, M. Absolute humidity modulates influenza survival, transmission, and seasonality. Proc. Natl Acad. Sci. USA 106, 3243–3248 (2009).
  CAS PubMed Google Scholar
• Young, L. C. et al. Summer outbreak of respiratory disease in an Australian prison due to an influenza A/Fujian/411/2002(H3N2)-like virus. Epidemiol. Infect. 133, 107–112 (2005).
  CAS PubMed PubMed Central Google Scholar
• Finnie, T. J. R., Copley, V. R., Hall, I. M. & Leach, S. An analysis of influenza outbreaks in institutions and enclosed societies. Epidemiol. Infect. 142, 107–113 (2014).
  CAS PubMed Google Scholar
• Gaillat, J., Dennetière, G., Raffin-Bru, E., Valette, M. & Blanc, M. C. Summer influenza outbreak in a home for the elderly: application of preventive measures. J. Hosp. Infect. 70, 272–277 (2008).
  CAS PubMed Google Scholar
• Cauchemez, S., Valleron, A.-J., Boëlle, P.-Y., Flahault, A. & Ferguson, N. M. Estimating the impact of school closure on influenza transmission from Sentinel data. Nature 452, 750–754 (2008).
  CAS PubMed Google Scholar
• Dopico, X. C. et al. Widespread seasonal gene expression reveals annual differences in human immunity and physiology. Nat. Commun. 6, 7000 (2015).
  CAS PubMed PubMed Central Google Scholar
• Hirsch, A. & Creighton, C. Handbook of geographical and historical pathology. (London: The New Sydenham Society, 1883).
  Google Scholar
• Hope-Simpson, R. E. The role of season in the epidemiology of influenza. J. Hyg. 86, 35–47 (1981).
  CAS PubMed Google Scholar
• Shortridge, K. F., Peiris, J. S. M. & Guan, Y. The next influenza pandemic: lessons from Hong Kong. J. Appl. Microbiol. 94 (Suppl.), 70S–79S (2003).
  PubMed Google Scholar
• Nelson, M. I., Simonsen, L., Viboud, C., Miller, M. A. & Holmes, E. C. Phylogenetic analysis reveals the global migration of seasonal influenza A viruses. PLoS Pathog. 3, e131 (2007).
  PubMed Central Google Scholar
• Russell, C. A. et al. The global circulation of seasonal influenza A (H3N2) viruses. Science 320, 340–346 (2008).
  CAS PubMed Google Scholar
• Rambaut, A. et al. The genomic and epidemiological dynamics of human influenza A virus. Nature 453, 615–619 (2008).
  CAS PubMed PubMed Central Google Scholar
• Chan, J., Holmes, A. & Rabadan, R. Network analysis of global influenza spread. PLoS Comput. Biol. 6, e1001005 (2010).
  PubMed PubMed Central Google Scholar
• Lemey, P. et al. Unifying viral genetics and human transportation data to predict the global transmission dynamics of human influenza H3N2. PLoS Pathog. 10, e1003932 (2014).
  PubMed PubMed Central Google Scholar
• Bielejec, F., Lemey, P., Baele, G., Rambaut, A. & Suchard, M. A. Inferring heterogeneous evolutionary processes through time: from sequence substitution to phylogeography. Syst. Biol. 63, 493–504 (2014).
  PubMed PubMed Central Google Scholar
• Bedford, T., Cobey, S., Beerli, P. & Pascual, M. Global migration dynamics underlie evolution and persistence of human influenza A (H3N2). PLoS Pathog. 6, e1000918 (2010).
  PubMed PubMed Central Google Scholar
• Bedford, T. et al. Integrating influenza antigenic dynamics with molecular evolution. eLife 3, e01914 (2014).
  PubMed PubMed Central Google Scholar
• Ferguson, N. M., Galvani, A. P. & Bush, R. M. Ecological and immunological determinants of influenza evolution. Nature 422, 428–433 (2003).
  CAS PubMed Google Scholar
• Partridge, J. & Kieny, M. P. Global production capacity of seasonal influenza vaccine in 2011. Vaccine 31, 728–731 (2013).
  PubMed Google Scholar
• Flannery, B. et al. Enhanced genetic characterization of influenza A(H3N2) Viruses and vaccine effectiveness by genetic group, 2014–2015. J. Infect. Dis. 214, 1010–1019 (2016).
  PubMed PubMed Central Google Scholar
• Skowronski, D. M. et al. A perfect storm: impact of genomic variation and serial vaccination on low influenza vaccine effectiveness during the 2014–2015 season. Clin. Infect. Dis. 63, 21–32 (2016).
  CAS PubMed PubMed Central Google Scholar
• WHO Writing Group 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 6, 142–152 (2012).
• de Jong, J. C., Beyer, W. E. P., Palache, A. M., Rimmelzwaan, G. F. & Osterhaus, A. D. M. E. Mismatch between the 1997/1998 influenza vaccine and the major epidemic A(H3N2) virus strain as the cause of an inadequate vaccine-induced antibody response to this strain in the elderly. J. Med. Virol. 61, 94–99 (2000).
  CAS PubMed Google Scholar
• Skowronski, D. M. et al. Low 2012–2013 influenza vaccine effectiveness associated with mutation in the egg-adapted H3N2 vaccine strain not antigenic drift in circulating viruses. PLoS ONE 9, e92153 (2014).
  PubMed PubMed Central Google Scholar
• Wong, S.-S. & Webby, R. J. Traditional and new influenza vaccines. Clin. Microbiol. Rev. 26, 476–492 (2013). This is an excellent review of the processes, challenges and future directions for influenza virus vaccine production.
  CAS PubMed PubMed Central Google Scholar
• Krammer, F. & Palese, P. Advances in the development of influenza virus vaccines. Nat. Rev. Drug Discov. 14, 167–182 (2015).
  CAS PubMed Google Scholar
• Brand, C. & Palese, P. Sequential passage of influenza virus in embryonated eggs or tissue culture: emergence of mutants. Virology 107, 424–433 (1980).
  CAS PubMed Google Scholar
• McWhite, C. D., Meyer, A. G. & Wilke, C. O. Sequence amplification via cell passaging creates spurious signals of positive adaptation in influenza virus H3N2 hemagglutinin. Virus Evol. 2, vew026 (2016).
  PubMed PubMed Central Google Scholar
• Łuksza, M. & Lässig, M. A predictive fitness model for influenza. Nature 507, 57–61 (2014).
  PubMed Google Scholar
• Neher, R. A., Russell, C. A. & Shraiman, B. I. Predicting evolution from the shape of genealogical trees. eLife 3, e03568 (2014).
  PubMed Central Google Scholar
• Neher, R. A., Bedford, T., Daniels, R. S., Russell, C. A. & Shraiman, B. I. Prediction, dynamics, and visualization of antigenic phenotypes of seasonal influenza viruses. Proc. Natl Acad. Sci. USA 113, E1701–E1709 (2016).
  CAS PubMed Google Scholar
• Neher, R. A. & Bedford, T. nextflu: real-time tracking of seasonal influenza virus evolution in humans. Bioinformatics 31, 3546–3548 (2015).
  CAS PubMed PubMed Central Google Scholar
• Nolan, T. et al. Safety and immunogenicity of a prototype adjuvanted inactivated split-virus influenza A (H5N1) vaccine in infants and children. Vaccine 26, 6383–6391 (2008).
  CAS PubMed Google Scholar
• Van Damme, P. et al. Long-term persistence of humoral and cellular immune responses induced by an AS03A-adjuvanted H1N1 2009 influenza vaccine: an open-label, randomized study in adults aged 18–60 years and older. Hum. Vaccin. Immunother. 9, 1512–1522 (2013).
  CAS PubMed Google Scholar
• Andrews, N. J. et al. Predictors of immune response and reactogenicity to AS03B-adjuvanted split virion and non-adjuvanted whole virion H1N1 pandemic influenza vaccines. Vaccine 29, 7913–7919 (2011).
  CAS PubMed Google Scholar
• Huijskens, E. et al. Immunogenicity, boostability, and sustainability of the immune response after vaccination against Influenza A virus (H1N1) 2009 in a healthy population. Clin. Vaccine Immunol. 18, 1401–1405 (2011).
  CAS PubMed PubMed Central Google Scholar
• Smith, D. J., Forrest, S., Ackley, D. H. & Perelson, A. S. Variable efficacy of repeated annual influenza vaccination. Proc. Natl Acad. Sci. USA 96, 14001–14006 (1999).
  CAS PubMed Google Scholar
• Skowronski, D. M. et al. Serial vaccination and the antigenic distance hypothesis: effects on influenza vaccine effectiveness during A(H3N2) epidemics in Canada, 2010–2011 to 2014–2015. J. Infect. Dis. 215, 1059–1099 (2017).
  PubMed PubMed Central Google Scholar
• Corti, D. et al. A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. Science 333, 850–856 (2011).
  CAS PubMed Google Scholar
• Tumpey, T. M., Renshaw, M., Clements, J. D. & Katz, J. M. Mucosal delivery of inactivated influenza vaccine induces B-cell-dependent heterosubtypic cross-protection against lethal influenza A H5N1 virus infection. J. Virol. 75, 5141–5150 (2001).
  CAS PubMed PubMed Central Google Scholar
• Hoft, D. F. et al. Comparisons of the humoral and cellular immune responses induced by live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) in adults. Clin. Vaccine Immunol. 24, e00414-16 (2016).
  Google Scholar
• Li, C. et al. Selection of antigenically advanced variants of seasonal influenza viruses. Nat. Microbiol. 1, 16058 (2016).
  CAS PubMed PubMed Central Google Scholar
• Leroux-Roels, I. et al. Antigen sparing and cross-reactive immunity with an adjuvanted rH5N1 prototype pandemic influenza vaccine: a randomised controlled trial. Lancet Lond. Engl. 370, 580–589 (2007).
  CAS Google Scholar
• Khurana, S. et al. Vaccines with MF59 adjuvant expand the antibody repertoire to target protective sites of pandemic avian H5N1 influenza virus. Sci. Transl. Med. 2, 15ra5 (2010).
  PubMed Google Scholar
• Lee, J. et al. Molecular-level analysis of the serum antibody repertoire in young adults before and after seasonal influenza vaccination. Nat. Med. 22, 1456–1464 (2016).
  CAS PubMed PubMed Central Google Scholar
• Jiang, N. et al. Lineage structure of the human antibody repertoire in response to influenza vaccination. Sci. Transl. Med. 5, 171ra19 (2013).
  PubMed PubMed Central Google Scholar
• Nakaya, H. I. et al. Systems biology of immunity to MF59-adjuvanted versus nonadjuvanted trivalent seasonal influenza vaccines in early childhood. Proc. Natl Acad. Sci. USA 113, 1853–1858 (2016).
  CAS PubMed Google Scholar
• Wang, C. et al. B-Cell repertoire responses to varicella-zoster vaccination in human identical twins. Proc. Natl Acad. Sci. USA 112, 500–505 (2015).
  CAS PubMed Google Scholar
• Boyd, S. D. & Jackson, K. J. L. Predicting vaccine responsiveness. Cell Host Microbe 17, 301–307 (2015).
  CAS PubMed Google Scholar
• Monto, A. S. & Maassab, H. F. Ether treatment of type B influenza virus antigen for the hemagglutination inhibition test. J. Clin. Microbiol. 13, 54–57 (1981).
  CAS PubMed PubMed Central Google Scholar
• Mosterín Höpping, A., Fonville, J. M., Russell, C. A., James, S. & Smith, D. J. Influenza B vaccine lineage selection — an optimized trivalent vaccine. Vaccine 34, 1617–1622 (2016).
  PubMed PubMed Central Google Scholar
• Heikkinen, T., Ikonen, N. & Ziegler, T. Impact of influenza B lineage-level mismatch between trivalent seasonal influenza vaccines and circulating viruses, 1999–2012. Clin. Infect. Dis. 59, 1519–1524 (2014).
  CAS PubMed Google Scholar
• Saito, T. et al. Antigenic alteration of influenza B virus associated with loss of a glycosylation site due to host-cell adaptation. J. Med. Virol. 74, 336–343 (2004).
  CAS PubMed Google Scholar
• WHO. FluNet. WHO http://www.who.int/influenza/gisrs_laboratory/flunet/en/ (2017).
• Rogers, M. B. et al. Intrahost dynamics of antiviral resistance in influenza A virus reflect complex patterns of segment linkage, reassortment, and natural selection. mBio 6, e02464-14 (2015).
  PubMed PubMed Central Google Scholar
• Russell, C. A. et al. The potential for respiratory droplet-transmissible A/H5N1 influenza virus to evolve in a mammalian host. Science 336, 1541–1547 (2012).
  CAS PubMed PubMed Central Google Scholar
• Österlund, P. et al. Incoming influenza A virus evades early host recognition, while influenza B virus induces interferon expression directly upon entry. J. Virol. 86, 11183–11193 (2012).
  PubMed PubMed Central Google Scholar
• Crotta, S. et al. Type I and type III interferons drive redundant amplification loops to induce a transcriptional signature in influenza-infected airway epithelia. PLoS Pathog. 9, e1003773 (2013).
  PubMed PubMed Central Google Scholar
• Miao, H. et al. Quantifying the early immune response and adaptive immune response kinetics in mice infected with influenza A virus. J. Virol. 84, 6687–6698 (2010).
  CAS PubMed PubMed Central Google Scholar
• Tas, J. M. J. et al. Visualizing antibody affinity maturation in germinal centers. Science 351, 1048–1054 (2016).
  CAS PubMed PubMed Central Google Scholar
• Choi, Y. S. & Baumgarth, N. Dual role for B-1a cells in immunity to influenza virus infection. J. Exp. Med. 205, 3053–3064 (2008).
  CAS PubMed PubMed Central Google Scholar
• Deenick, E. K. et al. Naive and memory human B cells have distinct requirements for STAT3 activation to differentiate into antibody-secreting plasma cells. J. Exp. Med. 210, 2739–2753 (2013).
  CAS PubMed PubMed Central Google Scholar
• Tinoco, J. C. et al. Immunogenicity, reactogenicity, and safety of inactivated quadrivalent influenza vaccine candidate versus inactivated trivalent influenza vaccine in healthy adults aged ≥18 years: a phase III, randomized trial. Vaccine 32, 1480–1487 (2014).
  CAS PubMed Google Scholar
• Gerdil, C. The annual production cycle for influenza vaccine. Vaccine 21, 1776–1779 (2003).
  PubMed Google Scholar
• Cox, R. J. et al. A phase I clinical trial of a PER. C6® cell grown influenza H7 virus vaccine. Vaccine 27, 1889–1897 (2009).
  CAS PubMed Google Scholar
• Kistner, O. et al. Development of a mammalian cell (Vero) derived candidate influenza virus vaccine. Vaccine 16, 960–968 (1998).
  CAS PubMed Google Scholar
• Dormitzer, P. R. Rapid production of synthetic influenza vaccines. Curr. Top. Microbiol. Immunol. 386, 237–273 (2015).
  CAS PubMed Google Scholar
• Cox, M. M. J. Recombinant protein vaccines produced in insect cells. Vaccine 30, 1759–1766 (2012).
  CAS PubMed Google Scholar
• Cox, M. M. J., Patriarca, P. A. & Treanor, J. FluBlok, a recombinant hemagglutinin influenza vaccine. Influenza Other Respir. Viruses 2, 211–219 (2008).
  PubMed PubMed Central Google Scholar
• Alexandrova, G. I. et al. Study of live recombinant cold-adapted influenza bivalent vaccine of type A for use in children: an epidemiological control trial. Vaccine 4, 114–118 (1986).
  CAS PubMed Google Scholar
• Rudenko, L., Isakova-Sivak, I. & Donina, S. H7N3 live attenuated influenza vaccine has a potential to protect against new H7N9 avian influenza virus. Vaccine 31, 4702–4705 (2013).
  CAS PubMed Google Scholar
• Ramezanpour, B., Pronker, E. S., Kreijtz, J. H. C. M., Osterhaus, A. D. M. E. & Claassen, E. Market implementation of the MVA platform for pre-pandemic and pandemic influenza vaccines: a quantitative key opinion leader analysis. Vaccine 33, 4349–4358 (2015).
  PubMed PubMed Central Google Scholar
• Altenburg, A. F. et al. Modified vaccinia virus ankara (MVA) as production platform for vaccines against influenza and other viral respiratory diseases. Viruses 6, 2735–2761 (2014).
  CAS PubMed PubMed Central Google Scholar
• Fries, L. F., Smith, G. E. & Glenn, G. M. A. Recombinant viruslike particle influenza A (H7N9) vaccine. N. Engl. J. Med. 369, 2564–2566 (2013).
  CAS PubMed Google Scholar
• Fiers, W. et al. M2e-based universal influenza A vaccine. Vaccine 27, 6280–6283 (2009).
  CAS PubMed Google Scholar
• Mallajosyula, V. V. A. et al. Influenza hemagglutinin stem-fragment immunogen elicits broadly neutralizing antibodies and confers heterologous protection. Proc. Natl Acad. Sci. USA 111, E2514–E2523 (2014).
  CAS PubMed Google Scholar