Seasonal Influenza Vaccine Effectiveness in Persons Aged 15–64 Years: A Systematic Review and Meta-Analysis

Influenza is a respiratory disease caused by the influenza virus, which is highly transmissible in humans. This paper presents a systematic review and meta-analysis of randomized controlled trials (RCTs) and test-negative designs (TNDs) to assess the vaccine effectiveness (VE) of seasonal influenza vaccines (SIVs) in humans aged 15 to 64 years. An electronic search to identify all relevant studies was performed. The outcome measure of interest was VE on laboratory-confirmed influenza (any strain). Quality assessment was performed using the Cochrane risk-of-bias tool for RCTs and the ROBINS-I tool for TNDs. The search identified a total of 2993 records, but only 123 studies from 73 papers were included in the meta-analysis. Of these studies, 9 were RCTs and 116 were TNDs. The pooled VE was 48% (95% CI: 42–54) for RCTs, 55.4% (95% CI: 43.2–64.9) when there was a match between the vaccine and most prevalent circulating strains and 39.3% (95% CI: 23.5–51.9) otherwise. The TNDs’ adjusted VE was equal to 39.9% (95% CI: 31–48), 45.1 (95% CI: 38.7–50.8) when there was a match and 35.1 (95% CI: 29.0–40.7) otherwise. The match between strains included in the vaccine and strains in circulation is the most important factor in the VE. It increases by more than 25% when there is a match with the most prevalent circulating strains. The laboratorial method for confirmation of influenza is a possible source of bias when estimating VE.