Repeated annual influenza vaccination and vaccine effectiveness: review of evidence

ABSTRACT

Introduction: Studies in the 1970s and 1980s signaled concern that repeated influenza vaccination could affect vaccine protection. The antigenic distance hypothesis provided a theoretical framework to explain variability in repeat vaccination effects based on antigenic similarity between successive vaccine components and the epidemic strain.

Areas covered: A meta-analysis of vaccine effectiveness studies from 2010–11 through 2014–15 shows substantial heterogeneity in repeat vaccination effects within and between seasons and subtypes. When negative effects were observed, they were most pronounced for H3N2, especially in 2014–15 when vaccine components were unchanged and antigenically distinct from the epidemic strain. Studies of repeated vaccination across multiple seasons suggest that vaccine effectiveness may be influenced by more than one prior season. In immunogenicity studies, repeated vaccination blunts the hemagglutinin antibody response, particularly for H3N2.

Expert commentary: Substantial heterogeneity in repeated vaccination effects is not surprising given the variation in study populations and seasons, and the variable effects of antigenic distance and immunological landscape in different age groups and populations. Caution is required in the interpretation of pooled results across multiple seasons, since this can mask important variation in repeat vaccination effects between seasons. Multi-season clinical studies are needed to understand repeat vaccination effects and guide recommendations.

KEYWORDS:

• Influenza
• vaccine
• effectiveness
• efficacy
• immunogenicity
• meta-analysis
• repeat
• recurrent

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Acknowledgements

The authors thank Lisan Kwindt (BC Centre for Disease Control) for data management support of the meta-analysis and Ursula Ellis (University of British Columbia) for assistance with the search strategy.

Declaration of interest

E Belongia and H Mclean received research support from MedImmune and U.S centers for Disease Control and Prevention. GD Serres received investigator- initiated grants from GSK and Pfizer, travel reimbursement to attend an ad hoc advisory board meeting of GSK and honorarium from the Ontario Nurse Association for providing expert testimony during legal challenge of enforced healthcare worker influenza vaccination. D Skowronski received funding from the Public Health Agency of Canada and the Bill & Melinda Gates foundation to convene the I-ReV (Influenza – Repeat Vaccination) Symposium held in Vancouver, British Columbia, Canada in October 2016 to support multi-disciplinary discussion of related epidemiological findings and their possible immunological mechanisms. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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This manuscript was not funded.