Change in the efficacy of influenza vaccination after repeated inoculation under antigenic mismatch: A systematic review and meta-analysis

Vaccine. 2018 Feb 8;36(7):949-957. doi: 10.1016/j.vaccine.2018.01.023. Epub 2018 Jan 17.


Objectives: To examine the effects of repeated influenza vaccination on medically-attended influenza (MAI) and acute respiratory illness (ARI) risk according to the antigenic matching between vaccine and circulating virus strains.

Methods: We performed a systematic review and meta-analysis of randomized studies that compared the risk of MAI and ARI between subjects who had been vaccinated for two consecutive seasons (multiple vaccine group) and those who had been vaccinated in the current season and not in the previous season (single vaccine group).

Results: Of 1467 articles identified, eight studies covering ten seasons were included in meta-analyses. Six studies assessed efficacy against MAI in children, yielding the risk ratios (RR) of 2.04 (95% CI 1.29-3.22) when circulating strains mismatched vaccine strains, and 0.64 (0.33-1.22) when circulating strains matched vaccine strains. When stratified by vaccine types, the reduced efficacy was significant for live-attenuated influenza vaccine only. Three studies investigated efficacy against ARI in children, with the RR of 0.96 (0.81-1.15). The results on adults and the elderly were scarce.

Conclusions: Influenza vaccine efficacy against mismatch strains was lower in repeatedly vaccinated children as compared with those vaccinated for the current season only. The scarcity of available studies may call for further randomized controlled trials on repeated influenza vaccination.

Keywords: Antigenic match; Children; Influenza vaccine; Natural infection; Repeated vaccination.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antigens, Viral / immunology*
  • Humans
  • Immunization, Secondary
  • Immunogenicity, Vaccine*
  • Influenza A virus / immunology*
  • Influenza Vaccines / immunology*
  • Influenza, Human / prevention & control*
  • Outcome Assessment, Health Care
  • Publication Bias
  • Randomized Controlled Trials as Topic
  • Vaccination*


  • Antigens, Viral
  • Influenza Vaccines