Does consecutive influenza vaccination reduce protection against influenza: A systematic review and meta-analysis.

INTRODUCTION: Vaccination against influenza on an annual basis is widely recommended, yet recent studies suggest consecutive vaccination may reduce vaccine effectiveness (VE). PURPOSE: To assess whether when examining the entirety of existing data consecutive influenza vaccination reduces VE compared to current season influenza vaccination. DATA SOURCES: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to April 26, 2017; citations of included studies. STUDY SELECTION: Randomized, controlled trials (RCTs) and observational studies of children, adults and/or the elderly that reported laboratory-confirmed influenza infection over 2 or more consecutive influenza seasons were eligible. DATA EXTRACTION: Data related to study characteristics, participant demographics, cases of influenza infection by vaccination group and risk of bias assessment was extracted in duplicate. DATA SYNTHESIS: Five RCTs involving 11,987 participants did not show a significant reduction in VE when participants vaccinated in two consecutive seasons (VE 71%, 95% CI 62-78%) were compared to those vaccinated in the current season (VE 58%, 95% CI 48-66%) (odds ratio [OR] 0.88, 95% CI 0.62-1.26, p = 0.49, I2 = 39%). Twenty-eight observational studies involving 28,627 participants also did not show a reduction (VE for two consecutive seasons 41%, 95% CI 30-51% compared to VE for current season 47%, 95% CI 39-54%; OR 1.14, 95% CI 0.98-1.32, p = 0.09, I2 = 63%). Results from subgroup analyses by influenza type/subtype, vaccine type, age, vaccine match and co-morbidity support these findings; however, dose-response results were inconsistent. Certainty in the evidence was assessed to be very low due to unexplained heterogeneity and imprecision. LIMITATIONS: The inclusion of studies with relatively small sample sizes and low event rates contributed to the imprecision of summary VE and OR estimates, which were based on unadjusted data. CONCLUSION: Available evidence does not support a reduction in VE with consecutive influenza vaccination, but the possibility of reduced effectiveness cannot be ruled out due to very low certainty in this evidence. FUNDING SOURCE: CIHR Foundation Grant (PROSPERO: CRD42017059893).