From the Journals

Flu susceptibility driven by birth year

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Imprinting could influence vaccination strategies

A growing body of epidemiological evidence points to the prolonged effects of cross-immunity, including competition between strains during seasonal and pandemic outbreaks, reduced risk of pandemic infection in those with previous seasonal exposure, and – as reported by Gostic et al. – lifelong protection against viruses of different subtypes but in the same hemagglutinin (HA) homology group. Basic science efforts are now needed to fully validate the HA imprinting hypothesis. More broadly, further experimental and theoretical work should map the relationship between early childhood exposure to influenza and immune protection and the implications of lifelong immunity for vaccination strategies and pandemic risk.

Cécile Viboud, PhD, is the acting director of the division of international epidemiology and population studies at the Fogarty International Center at the National Institutes of Health. Suzanne L. Epstein, PhD, is the associate director for research at the office of tissues and advanced therapies at the Food and Drug Administration Center for Biologics Evaluation and Research. They had no relevant financial disclosures and made these remarks in an editorial that accompanied the published study (Science. 2016 Nov 11;354[6313]:706-7. doi:10.1126/science.aak9816).


 

Differences in susceptibility to an influenza A virus (IAV) strain may be traceable to the first lifetime influenza infection, according to a new statistical model, which could have implications for epidemiology and future flu vaccines.

In the Nov. 11 issue of Science, researchers described infection models of the H5N1 and H7N9 strains of influenza A. The former occurs more commonly in younger people, and the latter in older individuals, but the reasons for those associations have puzzled scientists.

influenza, flu mik38/Fotolia.com

The researchers, led by James Lloyd-Smith, PhD, of the department of ecology and evolutionary biology at the University of California, Los Angeles, looked at susceptibility to IAV strains by birth year, and found that this was the best predictor of vulnerability. For example, an analysis of H5N1 cases in Egypt, where had many H5N1 cases spread over the past decade, showed that individuals born in the same year had the same average risk of severe H5N1 infection, even after they had aged by 10 years. That suggests that it is the birth year, not advancing age, which influences susceptibility (Science. 2016 Nov 11;354[6313]:721-5. doi:10.1126/science.aag1322).

The researchers suggest that the immune system “imprints” on the hemagglutinin (HA) subtype during an individual’s first infection, which confers protection against severe disease caused by other, related viruses, though it may not reduce infection rates overall.

The year 1968 may have marked an important inflection point. That year marked a shift in the identify of circulating viruses, from group 1 HA (which includes H5N1) to group 2 HA (which includes H7N9). Individuals born before 1968 were likely first infected with a group 1 virus, while those born later were most likely initially exposed to a group 2 virus. If the imprint theory is correct, younger people would have imprinted on group 2 viruses similar to H7N9, which would explain their greater vulnerability to group 1 viruses like H5N1.

“Imprinting was the dominant explanatory factor for observed incidence and mortality patterns for both H5N1 and H7N9. It was the only tested factor included in all plausible models for both viruses,” the researchers wrote.

According to the model, imprinting explains 75% of protection against severe infection and 80% of the protection against mortality for H5N1 and H7N9.

That information adds a previously unrecognized layer to influenza epidemiology, which should be accounted for in public health measures. “The methods shown here can provide rolling estimates of which age groups would be at highest risk for severe disease should particular novel HA subtypes emerge,” the researchers wrote.

The researchers received funding from the National Institutes of Health, the National Science Foundation, the David and Lucile Packard Foundation, and the Department of Homeland Security. They reported having no financial disclosures.

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