Lifelong protection against severe influenza

The first influenza attack that a child suffers can affect the way that their lifelong immunity to the virus builds up. A wide range of influenza A virus subtypes infect humans. Subtype H5 belongs to HA group 1 (which also includes H1 and H2 subtypes), and subtype H7 belongs to HA group 2 (which also includes the H3 subtype). Gostic et al. found that birth-year cohorts that experienced first infections with seasonal H3 subtype viruses were less susceptible to the potentially fatal avian influenza H7N9 virus (see the Perspective by Viboud and Epstein). Conversely, older individuals who were exposed to H1 or H2 subtype viruses as youngsters were less susceptible to avian H5N1-bearing viruses. A mathematical model of the protective effect of this imprinting could potentially prove useful to predict the age distribution and severity of future pandemics.
Science, this issue p. 722; see also p. 706


Two zoonotic influenza A viruses (IAV) of global concern, H5N1 and H7N9, exhibit unexplained differences in age distribution of human cases. Using data from all known human cases of these viruses, we show that an individual’s first IAV infection confers lifelong protection against severe disease from novel hemagglutinin (HA) subtypes in the same phylogenetic group. Statistical modeling shows that protective HA imprinting is the crucial explanatory factor, and it provides 75% protection against severe infection and 80% protection against death for both H5N1 and H7N9. Our results enable us to predict age distributions of severe disease for future pandemics and demonstrate that a novel strain’s pandemic potential increases yearly when a group-mismatched HA subtype dominates seasonal influenza circulation. These findings open new frontiers for rational pandemic risk assessment.

Get full access to this article

View all available purchase options and get full access to this article.

Already a subscriber or AAAS Member? Log In

Supplementary Material


Materials and Methods
Supplementary Text
Figs. S1 to S12
Tables S1 to S4
Database S1
References (3575)


File (
File (aag1322_gostic_sm.pdf)
File (table-s3-line-list-for-h7n9-cases-and-methods.xlsx)
File (table-s4-line-list-for-h5n1-cases-and-methods.xlsx)

References and Notes

Qin Y., Horby P. W., Tsang T. K., Chen E., Gao L., Ou J., Nguyen T. H., Duong T. N., Gasimov V., Feng L., Wu P., Jiang H., Ren X., Peng Z., Li S., Li M., Zheng J., Liu S., Hu S., Hong R., Farrar J. J., Leung G. M., Gao G. F., Cowling B. J., and Yu H., Differences in the epidemiology of human cases of avian influenza A(H7N9) and A(H5N1) viruses infection. Clin. Infect. Dis. 61, 563–571 (2015).
Cowling B. J., Jin L., Lau E. H. Y., Liao Q., Wu P., Jiang H., Tsang T. K., Zheng J., Fang V. J., Chang Z., Ni M. Y., Zhang Q., Ip D. K. M., Yu J., Li Y., Wang L., Tu W., Meng L., Wu J. T., Luo H., Li Q., Shu Y., Li Z., Feng Z., Yang W., Wang Y., Leung G. M., and Yu H., Comparative epidemiology of human infections with avian influenza A H7N9 and H5N1 viruses in China: A population-based study of laboratory-confirmed cases. Lancet 382, 129–137 (2013).
Kucharski A. J. and Edmunds W. J., Cross-immunity and age patterns of influenza A(H5N1) infection. Epidemiol. Infect. 143, 1119–1124 (2015).
Sandbulte M. R., Jimenez G. S., Boon A. C. M., Smith L. R., Treanor J. J., and Webby R. J., Cross-reactive neuraminidase antibodies afford partial protection against H5N1 in mice and are present in unexposed humans. PLOS Med. 4, e59 (2007).
Rivers C., Lum K., Lewis B., and Eubank S., Estimating Human Cases of Avian Influenza A(H7N9) from Poultry Exposure. PLOS Curr. 5, (2013).
Cowling B. J., Freeman G., Wong J. Y., Wu P., Liao Q., Lau E. H., Wu J. T., Fielding R., and Leung G. M., Preliminary inferences on the age-specific seriousness of human disease caused by avian influenza A(H7N9) infections in China, March to April 2013. Euro Surveill. 18, 20475 (2013).
Wang L., Cowling B. J., Wu P., Yu J., Li F., Zeng L., Wu J. T., Li Z., Leung G. M., and Yu H., Human exposure to live poultry and psychological and behavioral responses to influenza A(H7N9), China. Emerg. Infect. Dis. 20, 1296–1305 (2014).
Wrammert J., Koutsonanos D., Li G.-M., Edupuganti S., Sui J., Morrissey M., McCausland M., Skountzou I., Hornig M., Lipkin W. I., Mehta A., Razavi B., Del Rio C., Zheng N.-Y., Lee J.-H., Huang M., Ali Z., Kaur K., Andrews S., Amara R. R., Wang Y., Das S. R., O’Donnell C. D., Yewdell J. W., Subbarao K., Marasco W. A., Mulligan M. J., Compans R., Ahmed R., and Wilson P. C., Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection. J. Exp. Med. 208, 181–193 (2011).
Pica N., Hai R., Krammer F., Wang T. T., Maamary J., Eggink D., Tan G. S., Krause J. C., Moran T., Stein C. R., Banach D., Wrammert J., Belshe R. B., García-Sastre A., and Palese P., 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. 109, 2573–2578 (2012).
Li G.-M., Chiu C., Wrammert J., McCausland M., Andrews S. F., Zheng N.-Y., Lee J.-H., Huang M., Qu X., Edupuganti S., Mulligan M., Das S. R., Yewdell J. W., Mehta A. K., Wilson P. C., and Ahmed R., Pandemic H1N1 influenza vaccine induces a recall response in humans that favors broadly cross-reactive memory B cells. Proc. Natl. Acad. Sci. U.S.A. 109, 9047–9052 (2012).
Miller M. S., Gardner T. J., Krammer F., Aguado L. C., Tortorella D., Basler C. F., and Palese P., Neutralizing antibodies against previously encountered influenza virus strains increase over time: A longitudinal analysis. Sci. Transl. Med. 5, 198ra107 (2013).
Krammer F., Margine I., Hai R., Flood A., Hirsh A., Tsvetnitsky V., Chen D., and Palese P., H3 stalk-based chimeric hemagglutinin influenza virus constructs protect mice from H7N9 challenge. J. Virol. 88, 2340–2343 (2014).
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., Edupuganti S., Spearman P., Andrews S. F., Wilson P. C., García-Sastre A., Mulligan M. J., Mehta A. K., Palese P., and Ahmed R., Induction of broadly cross-reactive antibody responses to the influenza HA stem region following H5N1 vaccination in humans. Proc. Natl. Acad. Sci. U.S.A. 111, 13133–13138 (2014).
Palese P. and Wang T. T., Why do influenza virus subtypes die out? A hypothesis. MBio 2, e00150-11 (2011).
Francis T., On the doctrine of original antigenic sin. Proc. Am. Philos. Soc. 104, 572–578 (1960).
Lessler J., Riley S., Read J. M., Wang S., Zhu H., Smith G. J. D., Guan Y., Jiang C. Q., and Cummings D. A. T., Evidence for antigenic seniority in influenza A (H3N2) antibody responses in southern China. PLOS Pathog. 8, e1002802 (2012).
Smallman-Raynor M. and Cliff A. D., Avian influenza A (H5N1) age distribution in humans. Emerg. Infect. Dis. 13, 510–512 (2007).
Terajima M., Co M. D. T., and Ennis F. A., Age and different influenza viruses. Lancet Infect. Dis. 14, 101 (2014).
Worobey M., Han G.-Z., and Rambaut A., Genesis and pathogenesis of the 1918 pandemic H1N1 influenza A virus. Proc. Natl. Acad. Sci. U.S.A. 111, 8107–8112 (2014).
Sauerbrei A., Schmidt-Ott R., Hoyer H., and Wutzler P., Seroprevalence of influenza A and B in German infants and adolescents. Med. Microbiol. Immunol. (Berl.) 198, 93–101 (2009).
Sauerbrei A., Langenhan T., Brandstädt A., Schmidt-Ott R., Krumbholz A., Girschick H., Huppertz H., Kaiser P., Liese J., Streng A., Niehues T., Peters J., Sauerbrey A., Schroten H., Tenenbaum T., Wirth S., and Wutzler P., Prevalence of antibodies against influenza A and B viruses in children in Germany, 2008 to 2010. Euro Surveill. 19, 20687 (2014).
Laurie K. L., Carolan L. A., Middleton D., Lowther S., Kelso A., and Barr I. G., Multiple infections with seasonal influenza A virus induce cross-protective immunity against A(H1N1) pandemic influenza virus in a ferret model. J. Infect. Dis. 202, 1011–1020 (2010).
Schulman J. L. and Kilbourne E. D., Induction of partial specific heterotypic immunity in mice by a single infection with influenza A virus. J. Bacteriol. 89, 170–174 (1965).
Houser K. V., Pearce M. B., Katz J. M., and Tumpey T. M., Impact of prior seasonal H3N2 influenza vaccination or infection on protection and transmission of emerging variants of influenza A(H3N2)v virus in ferrets. J. Virol. 87, 13480–13489 (2013).
Wilkinson T. M., Li C. K. F., Chui C. S. C., Huang A. K. Y., Perkins M., Liebner J. C., Lambkin-Williams R., Gilbert A., Oxford J., Nicholas B., Staples K. J., Dong T., Douek D. C., McMichael A. J., and Xu X.-N., Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nat. Med. 18, 274–280 (2012).
Andrews S. F., Huang Y., Kaur K., Popova L. I., Ho I. Y., Pauli N. T., Henry Dunand C. J., Taylor W. M., Lim S., Huang M., Qu X., Lee J. H., Salgado-Ferrer M., Krammer F., Palese P., Wrammert J., Ahmed R., and Wilson P. C., Immune history profoundly affects broadly protective B cell responses to influenza. Sci. Transl. Med. 7, 316ra192 (2015).
Kohler I., Scherrer A. U., Zagordi O., Bianchi M., Wyrzucki A., Steck M., Ledergerber B., Günthard H. F., and Hangartner L., Prevalence and predictors for homo- and heterosubtypic antibodies against influenza a virus. Clin. Infect. Dis. 59, 1386–1393 (2014).
Sui J., Hwang W. C., Perez S., Wei G., Aird D., Chen L.-M., Santelli E., Stec B., Cadwell G., Ali M., Wan H., Murakami A., Yammanuru A., Han T., Cox N. J., Bankston L. A., Donis R. O., Liddington R. C., and Marasco W. A., Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat. Struct. Mol. Biol. 16, 265–273 (2009).
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., Ho I. Y., Taylor W., Hai R., Wrammert J., Ahmed R., García-Sastre A., Palese P., Krammer F., and Wilson P. C., Preexisting human antibodies neutralize recently emerged H7N9 influenza strains. J. Clin. Invest. 125, 1255–1268 (2015).
Mossong J., Hens N., Jit M., Beutels P., Auranen K., Mikolajczyk R., Massari M., Salmaso S., Tomba G. S., Wallinga J., Heijne J., Sadkowska-Todys M., Rosinska M., and Edmunds W. J., Social contacts and mixing patterns relevant to the spread of infectious diseases. PLOS Med. 5, e74 (2008).
Read J. M., Lessler J., Riley S., Wang S., Tan L. J., Kwok K. O., Guan Y., Jiang C. Q., and Cummings D. A. T., Social mixing patterns in rural and urban areas of southern China. Proc. Biol. Sci. 281, 20140268 (2014).
Horby P., Thai P. Q., Hens N., Yen N. T. T., Mai, L. Q., Thoang D. D., Linh N. M., Huong N. T., and Alexande N, rEdmunds W. J., Duong T. N., Fox A., and Hien N. T., Social contact patterns in Vietnam and implications for the control of infectious diseases. PLOS ONE 6, e16965 (2011).
Dauer C. C. and Serfling R. E., Mortality from influenza. Am. Rev. Respir. Dis. 83, 15–28 (1961).
Simonsen L., Reichert T. A., and Miller M. A., The virtues of antigenic sin: Consequences of pandemic recycling on influenza-associated mortality. Int. Congr. Ser. 1263, 791–794 (2004).
Chan P. K. S., Outbreak of avian influenza A(H5N1) virus infection in Hong Kong in 1997. Clin. Infect. Dis. 34 (suppl. 2), S58–S64 (2002).
Fiebig L., Soyka J., Buda S., Buchholz U., Dehnert M., and Haas W., Avian influenza A(H5N1) in humans: New insights from a line list of World Health Organization confirmed cases, September 2006 to August 2010. Euro Surveill. 16, 1–10 (2011).
Kucharski A., Mills H., Pinsent A., Fraser C., Van Kerkhove M., Donnelly C. A., and Riley S., Distinguishing between reservoir exposure and human-to-human transmission for emerging pathogens using case onset data. PLOS Curr. 6, ecurrents.outbreaks.e1473d9bfc99d080ca242139a06c455f (2014).
A. Kucharski, H. L. Mills, A. Pinsent, C. Fraser, M. Van Kerkhove, C. A. Donnelly, S. Riley, Data from: Distinguishing between reservoir exposure and human-to-human transmission for emerging pathogens using case onset data. (Dryad Digital Repository, 2014).
K. P. Burnham, D. R. Anderson, Model Selection and Multimodel Inference: A Practical Information-Theoretic Approach (Springer, New York, ed. 2, 2002).
U.S. Census Bureau, International Programs, International Data Base, (U.S. Census Bureau, Washington, DC, 2015);
Coates B. M., Staricha K. L., Wiese K. M., and Ridge K. M., Influenza A virus infection, innate immunity, and childhood. JAMA Pediatr. 169, 956–963 (2015).
Cromer D., van Hoek A. J., Jit M., Edmunds W. J., Fleming D., and Miller E., The burden of influenza in England by age and clinical risk group: A statistical analysis to inform vaccine policy. J. Infect. 68, 363–371 (2014).
M.-A. Widdowson, A. S. Monto, in Textbook of Influenza, R. G. Webster, A. S. Monto, T. J. Braciale, R. A. Lamb, Eds. (Wiley & Sons, Oxford, ed. 2, 2013), pp. 250–265.
Bodewes R., de Mutsert G., van der Klis F. R. M., Ventresca M., Wilks S., Smith D. J., Koopmans M., Fouchier R. A. M., Osterhaus A. D. M. E., and Rimmelzwaan G. F., Prevalence of antibodies against seasonal influenza A and B viruses in children in Netherlands. Clin. Vaccine Immunol. 18, 469–476 (2011).
Neuzil K. M., Zhu Y., Griffin M. R., Edwards K. M., Thompson J. M., Tollefson S. J., and Wright P. F., Burden of interpandemic influenza in children younger than 5 years: A 25-year prospective study. J. Infect. Dis. 185, 147–152 (2002).
Glezen W. P., Emerging infections: Pandemic influenza. Epidemiol. Rev. 18, 64–76 (1996).
Global Influenza Surveillance and Response System, “FluNet” (2015);
Thompson W. W., Shay D. K., Weintraub E., Brammer L., Cox N., Anderson L. J., and Fukuda K., Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 289, 179–186 (2003).
Palache A., Oriol-Mathieu V., Fino M., Xydia-Charmanta M., and Influenza Vaccine Supply task force (IFPMA IVS), Seasonal influenza vaccine dose distribution in 195 countries (2004-2013): Little progress in estimated global vaccination coverage. Vaccine 33, 5598–5605 (2015).
Kearse M., Moir R., Wilson A., Stones-Havas S., Cheung M., Sturrock S., Buxton S., Cooper A., Markowitz S., Duran C., Thierer T., Ashton B., Meintjes P., and Drummond A., Geneious Basic: An integrated and extendable desktop software platform for the organization and analysis of sequence data. Bioinformatics 28, 1647–1649 (2012).
Stamatakis A., RAxML-VI-HPC: Maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. Bioinformatics 22, 2688–2690 (2006).
Fraser C., Cummings D. A. T., Klinkenberg D., Burke D. S., and Ferguson N. M., Influenza transmission in households during the 1918 pandemic. Am. J. Epidemiol. 174, 505–514 (2011).
Mills C. E., Robins J. M., and Lipsitch M., Transmissibility of 1918 pandemic influenza. Nature 432, 904–906 (2004).
Fraser C., Donnelly C. A., Cauchemez S., Hanage W. P., Van Kerkhove M. D., Hollingsworth T. D., Griffin J., Baggaley R. F., Jenkins H. E., Lyons E. J., Jombart T., Hinsley W. R., Grassly N. C., Balloux F., Ghani A. C., Ferguson N. M., Rambaut A., Pybus O. G., Lopez-Gatell H., Alpuche-Aranda C. M., Chapela I. B., Zavala E. P., Guevara D. M. E., Checchi F., Garcia E., Hugonnet S., Roth C., and WHO Rapid Pandemic Assessment Collaboration, Pandemic potential of a strain of influenza A (H1N1): Early findings. Science 324, 1557–1561 (2009).
Viboud C., Tam T., Fleming D., Handel A., Miller M. A., and Simonsen L., Transmissibility and mortality impact of epidemic and pandemic influenza, with emphasis on the unusually deadly 1951 epidemic. Vaccine 24, 6701–6707 (2006).
White L. F., Wallinga J., Finelli L., Reed C., Riley S., Lipsitch M., and Pagano M., Estimation of the reproductive number and the serial interval in early phase of the 2009 influenza A/H1N1 pandemic in the USA. Influenza Other Respir. Viruses 3, 267–276 (2009).
Yang Y., Sugimoto J. D., Halloran M. E., Basta N. E., Chao D. L., Matrajt L., Potter G., Kenah E., and Longini I. M. Jr., The transmissibility and control of pandemic influenza A (H1N1) virus. Science 326, 729–733 (2009).
Cowling B. J., Fang V. J., Riley S., Malik Peiris J. S., and Leung G. M., Estimation of the serial interval of influenza. Epidemiology 20, 344–347 (2009).
Public Health England, Influenza: The Green Book, chapter 19 (Public Health England, London, version 10, 2015);
Public Health England, “The National Childhood Flu Immunisation Programme 2016/17: Information for healthcare practitioners” (2016);
Public Health England, “Seasonal influenza vaccine uptake amongst GP patients in England provisional monthly data for 1 September 2014 to 31 January 2015” (Public Health England, London, 2015);
Blank P. R., Schwenkglenks M., and Szucs T. D., Influenza vaccination coverage rates in five European countries during season 2006/07 and trends over six consecutive seasons. BMC Public Health 8, 272 (2008).
Public Health England, “Seasonal flu vaccine uptake in children of primary school age: Winter season 2015 to 2016” (2016);
Owusu J. T., Prapasiri P., Ditsungnoen D., Leetongin G., Yoocharoen P., Rattanayot J., Olsen S. J., and Muangchana C., Seasonal influenza vaccine coverage among high-risk populations in Thailand, 2010-2012. Vaccine 33, 742–747 (2015).
Kittikraisak W., Suntarattiwong P., Levy J., Fernandez S., Dawood F. S., Olsen S. J., and Chotpitayasunondh T., Influenza vaccination coverage and effectiveness in young children in Thailand, 2011-2013. Influenza Other Respir. Viruses 9, 85–93 (2015).
Zhou L., Su Q., Xu Z., Feng A., Jin H., Wang S., and Feng Z., Seasonal influenza vaccination coverage rate of target groups in selected cities and provinces in China by season (2009/10 to 2011/12). PLOS ONE 8, e73724 (2013).
Lau J. T. F., Mo P. K. H., Cai Y. S., Tsui H. Y., and Choi K. C., Coverage and parental perceptions of influenza vaccination among parents of children aged 6 to 23 months in Hong Kong. BMC Public Health 13, 1026 (2013).
Centers for Disease Control and Prevention, “Influenza vaccination coverage among children aged 6–23 months—United States, 2008–09 influenza season” (2010);
Allison M. A., Daley M. F., Crane L. A., Barrow J., Beaty B. L., Allred N., Berman S., and Kempe A., Influenza vaccine effectiveness in healthy 6- to 21-month-old children during the 2003-2004 season. J. Pediatr. 149, 755–762 (2006).
Housworth J. and Langmuir A. D., Excess mortality from epidemic influenza, 1957-1966. Am. J. Epidemiol. 100, 40–48 (1974).
Olson D. R., Simonsen L., Edelson P. J., and Morse S. S., Epidemiological evidence of an early wave of the 1918 influenza pandemic in New York City. Proc. Natl. Acad. Sci. U.S.A. 102, 11059–11063 (2005).
G. R. Noble, in Basic and Applied Influenza Research, A. S. Beare, Ed. (CRC Press, Boca Raton, FL, 1982), pp. 11–50.
Gover M., Influenza and Pneumonia Mortality in a Group of 90 Cities in the United States, August 1935-March 1943, with a Summary for August 1920-March 1943. Public Health Rep. 58, 1033–1061 (1943).
Collins S. D. and Lehmann J., Trends and epidemics of influenza and pneumonia: 1918-1951. Public Health Rep. 66, 1487–1516 (1951).
Alling D. W., Blackwelder W. C., and Stuart-Harris C. H., A study of excess mortality during influenza epidemics in the United States, 1968-1976. Am. J. Epidemiol. 113, 30–43 (1981).

Information & Authors


Published In

Volume 354 | Issue 6313
11 November 2016

Submission history

Received: 14 May 2016
Accepted: 3 October 2016
Published in print: 11 November 2016


Request permissions for this article.


We thank the Lloyd-Smith lab and the Worobey lab for helpful comments, C. Viboud for providing insight into historic influenza data, T. Mega and S. Wu for assistance compiling data, B. Cowling for sharing poultry exposure data, and P. Horby for sharing Vietnam contact data. K.M.G. is supported by the National Institute of General Medical Sciences of the National Institutes of Health (T32GM008185). M.A. is supported by the National Science Foundation Graduate Research Fellowship (DGE-1144087). M.W. is supported by the David and Lucile Packard Foundation. J.O.L-S. is supported by the National Science Foundation (EF-0928690); the Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directorate, Department of Homeland Security; and Fogarty International Center, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare no competing financial interests. Case data and code for model fitting are available as supplementary data files. Requests for materials should be addressed to M.W. or J.O.L.-S.



Katelyn M. Gostic
Department of Ecology and Evolutionary Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Monique Ambrose
Department of Ecology and Evolutionary Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Michael Worobey* [email protected]
Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA.
James O. Lloyd-Smith* [email protected]
Department of Ecology and Evolutionary Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA.


Corresponding author. Email: [email protected] (M.W.); [email protected] (J.O.L.-S.)

Metrics & Citations


Article Usage


Export citation

Select the format you want to export the citation of this publication.

Cited by

  1. Anomalous influenza seasonality in the United States and the emergence of novel influenza B viruses, Proceedings of the National Academy of Sciences, 118, 5, (e2012327118), (2021).
  2. Humoral and cellular immune responses in critically ill influenza A/H1N1‐infected patients, Scandinavian Journal of Immunology, 94, 2, (2021).
  3. Signatures of immune dysfunction in HIV and HCV infection share features with chronic inflammation in aging and persist after viral reduction or elimination, Proceedings of the National Academy of Sciences, 118, 14, (e2022928118), (2021).
  4. Seasonal influenza vaccination does not effectively expand H2 cross-reactive antibodies in humans, Vaccine, 39, 30, (4173-4183), (2021).
  5. Polyclonal epitope mapping reveals temporal dynamics and diversity of human antibody responses to H5N1 vaccination, Cell Reports, 34, 4, (108682), (2021).
  6. Aging-induced fragility of the immune system, Journal of Theoretical Biology, 510, (110473), (2021).
  7. Local memory CD4 T cell niches in respiratory viral infection, Journal of Experimental Medicine, 218, 8, (2021).
  8. Broadly Reactive H2 Hemagglutinin Vaccines Elicit Cross-Reactive Antibodies in Ferrets Preimmune to Seasonal Influenza A Viruses, mSphere, 6, 2, (2021).
  9. Lineage-specific protection and immune imprinting shape the age distributions of influenza B cases, Nature Communications, 12, 1, (2021).
  10. Modeling the selective advantage of new amino acids on the hemagglutinin of H1N1 influenza viruses using their patient age distributions, Virus Evolution, 7, 1, (2021).
  11. See more

View Options

Check Access

Log in to view the full text


AAAS login provides access to Science for AAAS Members, and access to other journals in the Science family to users who have purchased individual subscriptions.

Log in via OpenAthens.
Log in via Shibboleth.
More options

Register for free to read this article

As a service to the community, this article is available for free. Login or register for free to read this article.

Purchase this issue in print

Buy a single issue of Science for just $15 USD.

View options

PDF format

Download this article as a PDF file

Download PDF







Share article link

Share on social media