Repeated Influenza Vaccination Could Reduce Effectiveness

Indoor shot of vaccine test samples – with reflections of glass vials and syringe
Researchers assessed the impact on pooled adjusted end-season vaccine effectiveness estimates from outpatient test-negative design studies.

Seasonal influenza vaccine effectiveness declines with vaccination program maturation, defined as the number of years since program inception, according to a systematic review and meta-analysis published in Open Forum Infectious Diseases.

There is evidence that repeated influenza vaccination may reduce effectiveness. Investigators used program maturation as a proxy for population-level repeated vaccination and assessed the impact on pooled adjusted end-season vaccine effectiveness estimates from outpatient test-negative design studies.

In total, the researchers included 72 articles in their review and analysis. In these studies, program maturation ranged from 1 to 64 years; 59 studies were from the Northern hemisphere and 13 studies the Southern hemisphere.

The investigators found lower pooled vaccine effectiveness with program maturation. However, there was high heterogeneity across 3 categories of program maturation (cut at the median, tertiles, and quartiles).  Antigenic similarity with circulating strains was a possible explanation for the heterogeneity (P <.001). Similar observations were made in the analyses of all patients across the 3 categories but with less heterogeneity. There were higher reductions in effectiveness in older patients and similar results for A(H1N1)pdm09, A(H3N2), and influenza B were also observed.

Investigators conclude that no matter the categorization of program maturation, they observe a “largely consistent trend.” However, they advise cautious interpretation due to study limitations and potential confounders. The articles included in the analysis had different enrollment criteria, influenza status definitions, and respiratory specimen types. Sample size and statistical models also varied.

Study authors highlight the nature of the ecological data, the impact of differences in characteristics like age, sex, comorbidity status, prior history of influenza vaccination as well as the “healthy vaccinee” effect across studies as a significant weakness of the review. Further, the impacts of different vaccination rates across studies could not be assessed and a lack of data on some outcomes limited statistical analysis.

The uniqueness of this work is a strength, noted the investigators, and it is the first to investigate impact of seasonal vaccination program maturation on effectiveness. They believe this work will form the basis of further discussions and evaluations of program maturation, but it does not justify curbing or halting national vaccination programs.

Disclosures: Two authors declared affiliations with pharmaceutical companies. Please refer to the original article for a full list of disclosures.


Okoli GN, Racovitan F, Abdulwahid T, et al. Decline in seasonal influenza vaccine effectiveness with vaccination program maturation: A systematic review and meta-analysis. Open Forum Infect Dis. 2021;8(3):ofab069. doi: 10.1093/ofid/ofab069

This article originally appeared on Infectious Disease Advisor