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Meta-Analysis
. 2023 Jan;11(1):27-44.
doi: 10.1016/S2213-2600(22)00266-1. Epub 2022 Sep 21.

Does repeated influenza vaccination attenuate effectiveness? A systematic review and meta-analysis

Elenor Jones-Gray  1 , Elizabeth J Robinson  1 , Adam J Kucharski  2 , Annette Fox  3 , Sheena G Sullivan  4
Affiliations
Meta-Analysis

Does repeated influenza vaccination attenuate effectiveness? A systematic review and meta-analysis

Elenor Jones-Gray et al. Lancet Respir Med. 2023 Jan.

Abstract

Background: Influenza vaccines require annual readministration; however, several reports have suggested that repeated vaccination might attenuate the vaccine's effectiveness. We aimed to estimate the reduction in vaccine effectiveness associated with repeated influenza vaccination.

Methods: In this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and CINAHL Complete databases for articles published from Jan 1, 2016, to June 13, 2022, and Web of Science for studies published from database inception to June 13, 2022. For studies published before Jan 1, 2016, we consulted published systematic reviews. Two reviewers (EJ-G and EJR) independently screened, extracted data using a data collection form, assessed studies' risk of bias using the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I) and evaluated the weight of evidence by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). We included observational studies and randomised controlled trials that reported vaccine effectiveness against influenza A(H1N1)pdm09, influenza A(H3N2), or influenza B using four vaccination groups: current season; previous season; current and previous seasons; and neither season (reference). For each study, we calculated the absolute difference in vaccine effectiveness (ΔVE) for current season only and previous season only versus current and previous season vaccination to estimate attenuation associated with repeated vaccination. Pooled vaccine effectiveness and ∆VE were calculated by season, age group, and overall. This study is registered with PROSPERO, CRD42021260242.

Findings: We identified 4979 publications, selected 681 for full review, and included 83 in the systematic review and 41 in meta-analyses. ΔVE for vaccination in both seasons compared with the current season was -9% (95% CI -16 to -1, I2=0%; low certainty) for influenza A(H1N1)pdm09, -18% (-26 to -11, I2=7%; low certainty) for influenza A(H3N2), and -7% (-14 to 0, I2=0%; low certainty) for influenza B, indicating lower protection with consecutive vaccination. However, for all types, A subtypes and B lineages, vaccination in both seasons afforded better protection than not being vaccinated.

Interpretation: Our estimates suggest that, although vaccination in the previous year attenuates vaccine effectiveness, vaccination in two consecutive years provides better protection than does no vaccination. The estimated effects of vaccination in the previous year are concerning and warrant additional investigation, but are not consistent or severe enough to support an alternative vaccination regimen at this time.

Funding: WHO and the US National Institutes of Health.

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Conflict of interest statement

Declaration of interests SGS and AF report the following funding for influenza vaccination and infection studies: US National Institutes of Health (SGS and AF); US Centers for Disease Control (SGS and AF); the National Health and Medical Research Council of Australia (AF); and OptumLabs research credits (SGS). SGS and AF are employed by the WHO Collaborating Centre for Reference and Research on Influenza, which receives funding from the International Federation of Pharmaceutical Manufacturers and Associations and Seqiris for the development of influenza vaccines. SGS has served in an unpaid capacity on advisory boards for Sanofi and Seqiris. From 2017–21, SGS was a member of the WHO Strategic Advisory Group of Experts (SAGE) on Immunization Working Group on Influenza. SGS serves on the Australian National Influenza Surveillance Committee. EJ-G, EJR, and AJK declare no competing interests.

Figures

Figure 1
Figure 1
Study selection
Figure 2
Figure 2
Pooled vaccine effectiveness estimates against influenza A(H1N1)pdm09 for people vaccinated in the current season only, and current and previous seasons, and the difference in these estimates The reference group is people vaccinated in neither season. The previous season is defined as the influenza season immediately before the current season. The absolute difference in vaccine effectiveness (ΔVE) for people who were vaccinated in the current and previous (VECP) seasons and those vaccinated in the current season only (VEC) was calculated as: ΔVE = VECP– VEC. Random-effect models for each vaccination group are presented pooled by current season and across all seasons; see appendix (p 42) for fixed-effect estimates. Fixed-effect models are only presented for pooled estimates across all seasons; for season-specific fixed-effect estimates see appendix (p 42). NR=not reported. RE model=random-effect model estimate. ΔVE=change in vaccine effectiveness.
Figure 3
Figure 3
Pooled vaccine effectiveness estimates against influenza A(H3N2) for people vaccinated in the current season only, and current and previous seasons, and the difference in these estimates The reference group is people vaccinated in neither season. The previous season is defined as the influenza season immediately before the current season. The absolute difference in vaccine effectiveness (ΔVE) for people who were vaccinated in the current and previous (VECP) seasons and for those vaccinated in the current season only (VEC) was calculated as: ΔVE = VECP– VEC. Random-effect models for each vaccination group are presented pooled by current season and across all seasons. Fixed-effect models are only presented for pooled estimates across all seasons; for season-specific fixed-effect estimates see appendix (p 46). NR=not reported. RE model=random-effect model estimate. ΔVE=change in vaccine effectiveness. *Unadjusted vaccine effectiveness estimates are only presented in study.
Figure 4
Figure 4
Pooled vaccine effectiveness estimates against influenza B of any lineage for people vaccinated in the current season only, and current and previous seasons, and the difference in these estimates The reference group is people vaccinated in neither season. The previous season is defined as the influenza season immediately before the current season. The absolute difference in vaccine effectiveness (ΔVE) for people who were vaccinated in the current and previous (VECP) seasons and for those vaccinated in the current season only (VEC) was calculated as: ΔVE = VECP– VEC. Random-effect models for each vaccination group are presented pooled by current season, across all seasons, and by seasons by influenza B antigen included in the trivalent influenza vaccines. Fixed-effect models are presented for pooled estimates across all seasons; for season-specific fixed-effect estimates see appendix (p 50). NR=not reported. RE model=random-effect model estimate. ΔVE=change in vaccine effectiveness.
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