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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

Abstract

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.

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Supplementary Material

Summary

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

Resources

File (aag1322-database-s1.zip)
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)

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Science
Volume 354 | Issue 6313
11 November 2016

Submission history

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

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Acknowledgments

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.

Authors

Affiliations

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.

Notes

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

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