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Birth cohort affected 2015-2016 flu vaccine effectiveness

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Early influenza encounters could influence vaccine response

This study proposes that influenza virus strains encountered early in life focus the immune response to later infection or vaccination on shared epitopes between the early and later strains. Supporting this hypothesis is evidence from other studies showing that 60% of the serological response to inactivated influenza vaccines is the result of boosting pre-existing antibodies, rather than the creation of new, vaccine-induced antibodies.

However there are also some flaws to this argument, and we should be careful to avoid confirmation bias. For example, the reduction in effectiveness of vaccines against A(H1N1) has been observed in North America, where this study is located, but to a lesser extent in studies conducted in other regions. Reductions in vaccine effectiveness have also been observed in other birth cohorts and during other influenza seasons.

That aside, accumulating evidence suggests that the vaccine strain be updated from A/California/7/2009 to A/Michigan/45/2015 (a clade 6B.1 strain) for the 2016-2017 influenza seasons.

Allen C. Cheng, PhD, is from the School of Public Health and Preventive Medicine at Monash University, Melbourne, and Kanta Subbarao, MBBS, is from the World Health Organization Collaborating Centre for Reference and Research on Influenza and the Peter Doherty Institute for Infection and Immunity, Australia. These comments are taken from an accompanying editorial (J Infect Dis. 2018, Jan 18. doi: 10.1093/infdis/jix635). The authors declared support from the Australian Department of Health and the Australian National Health and Medical Research Council. No conflicts of interest were declared.



The influenza vaccine introduced in 2009 showed reduced effectiveness during the 2015-2016 influenza season, but only in adults born between 1958 and 1979, according to an analysis published online in the Journal of Infectious Diseases.

Overall, 48% of the influenza virus–negative patients and 28% of the virus-positive patients had received at least one dose of the seasonal inactivated influenza vaccine more than 2 weeks before they fell ill.

However, the vaccine, which was based on the A/California/07/2009 strain of the A(H1N1)pdm09 virus, was only 47% effective during the 2015-2016 season, compared with 61% effectiveness during the 2010-2011 season through to the 2013-2014 season.

When researchers looked at vaccine effectiveness by birth cohort, they found that one particular cohort – individuals born between 1958 and 1979 – showed a significantly reduced vaccine effectiveness (22%) during the 2015-2016 season. By comparison, vaccine effectiveness in this cohort was 61% during the 2010-2013 seasons, and 56% during the 2013-2014 season.

When this birth cohort was excluded from analysis of the 2015-2016 season, the overall vaccine effectiveness for that season was 61%.

While the vaccine was based on an early reference strain of A(H1N1)pdm09, the virus itself later acquired mutations in the hemagglutinin gene, leading to the emergence of new genetic clades, including 6B, which dominated in the 2013-2014 influenza season, and 6B.1, which dominated in 2015-2016.

“Limited serologic data suggest that some adults born during 1958-1979 (age range in 2015-2016, 36-57 years) have decreased antibody titers against A(H1N1)pdm09 group 6B and 6B.1 viruses,” wrote Brendan Flannery, PhD, from the Centers for Disease Control and Prevention, and his coauthors.

They suggested that individuals in this cohort may have been immunologically primed with A/USSR/90/1977-like viruses, which were the first group of A(H1N1) viruses that this cohort would have been exposed to. A(H1N1) strains didn’t circulate between 1958 and 1977. Vaccination with A(H1N1)pdm09 viruses may have induced antibodies against shared antigenic components found on early versions of A(H1N1)pdm09.

If these shared antigenic epitopes were then altered in the later 6B and 6B.1 viruses, that might account for decreased antibody titers in this age group.

“Replacement of the A/California/07/2009(H1N1)pdm09 vaccine reference strain with A/Michigan/45/2015 (group 6B.1) should lead to improved [vaccine effectiveness] against circulating A(H1N1)pdm09 viruses,” the investigators noted.

The study was supported by the Centers for Disease Control and Prevention, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Eight authors declared funding, grants, and consultancies with the pharmaceutical industry, with five also declaring funding from the CDC.

SOURCE: Flannery B et al. J Infect Dis. 2018 Jan 18. doi: 10.1093/infdis/jix634.

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