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Repeated Vaccination May Protect Children From Influenza Infection.

Influenza infections in children are problematic not only for the immediate symptoms they cause but also for their potentially large contribution to influenza infections in other age groups. Since 2008, the Advisory Committee on Immunization Practices has recommended that all children at least 6 months old be vaccinated annually against influenza. By historical standards, vaccination coverage in children in the United States is high, with nearly 60% of children younger than age 18 years and 76% of children aged 6 to 23 months receiving an influenza vaccine in the 2016-2017 season.1 Vaccination coverage in children has also expanded in the United Kingdom, where indirect benefits on other age groups have been observed.2 The recent expansion of vaccination coverage has coincided with increased attention to the vexing problem of why the vaccine is not more effective, and especially to scattered observations that the vaccine may be less effective in frequent recipients.3 Although many analyses of repeated vaccination included children in their study populations, they were underpowered to examine effects by age, and their statistical conclusions were inevitably heavily influenced by adults. Young children and adults can respond to vaccines differently, however, partly because they share different exposure histories. The study by McLean et al4 fills an important gap by measuring the association of repeated vaccination with vaccine effectiveness in children. From the 2013-2014 to the 2015-2016 seasons, the investigators enrolled 3369 children presenting with an acute respiratory illness at 4 sites in the United States. Using a retrospective, test-negative case-control design, the authors then estimated the ratio of vaccinated to unvaccinated children among the influenza test–positive cases and the same ratio among the influenza test–negative cases. The ratio of these ratios yields the exposure odds ratio of vaccination associated with being an influenza case and is one measure of vaccine effectiveness. The authors examined whether vaccine effectiveness changed with individuals’ recent histories of influenza vaccination while adjusting for sex, age group, and other factors. In no case was repeated vaccination associated with lower effectiveness than vaccination in the current season only. In other words, there was no evidence of diminished vaccine effectiveness in frequent vaccinees, even though the study included seasons in which such effects had been reported elsewhere. But there were intriguing differences in the effects of vaccination history by type. For influenza B, vaccination at any time—this season, last season, or both—was associated with similar effectiveness. This points to a high degree of residual protection for the B component of both the live attenuated influenza vaccines (LAIV) and inactivated influenza vaccines (IIV), which the study was able to examine separately. For influenza A(H3N2), prior vaccination appeared to enhance the effectiveness of LAIV. In this study influenza A(H3N2) cases occurred primarily in 2014-2015, a season in which a well-described antigenic mismatch lowered vaccine effectiveness.5 Notably, significant protection against influenza A(H3N2) in children vaccinated with LAIV was only associated with previous vaccination, and prior vaccination with IIV was associated with higher effectiveness. The effects of repeated vaccination with LAIV were thus in the opposite direction of what had been found in some older populations that season.3,6 Prior vaccination had no significant effect on the effectiveness of IIV against influenza A(H3N2), but like LAIV, the highest effectiveness was observed in repeated vaccinees. With influenza A(H1N1)pdm09, which circulated in the 2013-2014 and 20152016 seasons, IIV and LAIV were not significantly associated with vaccination history, but for LAIV, effectiveness was significantly associated with repeat vaccinees only. + Related article