title: Potent protection against H5N1 and H7N9 influenza via childhood hemagglutinin imprinting.
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.
authors.affiliation: Department of Ecology and Evolutionary Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Katelyn M
authors.initials: KM
authors.lastname: Gostic
authors.affiliation: Department of Ecology and Evolutionary Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Monique
authors.initials: M
authors.lastname: Ambrose
authors.affiliation: Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA. worobey@email.arizona.edu jlloydsmith@ucla.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Worobey
authors.affiliation: Department of Ecology and Evolutionary Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA. worobey@email.arizona.edu jlloydsmith@ucla.edu.|Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: James O
authors.initials: JO
authors.lastname: Lloyd-Smith
mesh_terms: D000367:Age Factors; D000818:Animals; D002648:Child; D018392:Genomic Imprinting; D014943:Global Health; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000276:immunology; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics* / Q000276:immunology; D064766:Influenza A Virus, H7N9 Subtype / Q000235:genetics* / Q000276:immunology; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D015233:Models, Statistical; D058873:Pandemics / Q000706:statistics & numerical data*; D018570:Risk Assessment; D015047:Zoonoses / Q000453:epidemiology / Q000821:virology
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus