Research Article

Potent protection against H5N1 and H7N9 influenza via childhood hemagglutinin imprinting

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Science  11 Nov 2016:
Vol. 354, Issue 6313, pp. 722-726
DOI: 10.1126/science.aag1322

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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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