Background Vaccine efficacy may vary due to influenza strain types, their similarity, and vaccine type. The relationship between immunological surrogate endpoints and vaccine efficacy remains unclear, requiring further investigation to optimize vaccination strategies. Objective This systematic review aims to address two key issues. First, to evaluate the vaccine efficacy stratified by vaccine types and virus strains. Second, to explore the quantitative relationship between immunological surrogate endpoints and vaccine efficacy. Data sources We searched PubMed, Embase, and ClinicalTrials.gov databases. Study eligibility criteria, patients, and interventions We included randomized controlled trials (RCTs) published on 16 July 2024, that evaluated the efficacy of influenza vaccines against laboratory-confirmed influenza. Phase I/II clinical trials, abstracts, reviews, unregistered trials, duplicate studies, and studies lacking original data or efficacy results were excluded. Methods This systematic review evaluates influenza vaccine efficacy and immunogenicity, including RCTs with outcomes like geometric mean titre (GMT), seroprotection, and seroconversion rates. Data were extracted from multiple databases and assessed using Cochrane and Grading of Recommendations Assessment, Development and Evaluation (GRADE) frameworks. Results Twenty-six RCTs (104 931 participants) were included. Pooled vaccine efficacy against laboratory-confirmed influenza was 48.48% (95% CI, 41.9–54.29), with significant heterogeneity (I<sup>2</sup> = 70.1%; p < 0.0001). Inactivated influenza vaccines had the highest vaccine efficacy (54.70%). Among different strains, the vaccine efficacy against H1N1 was the highest, reaching 59.38% (95% CI, 24.60–78.12). We found a significant nonlinear relationship between standardized mean difference (SMD) in hemagglutination antibody titre (HAI) concentration and vaccine efficacy against symptomatic infections, but with low explanatory power, and seroconversion rates, seroprotection rates, and fold increase in GMT were strongly associated with viral attack rates with Medium explanatory power (p < 0.05 for all), with explanatory values of 0.5038, 0.464, and 0.286, respectively. Discussion This systematic review highlights that influenza vaccines provide moderate protection, whereas the inactivated influenza vaccine demonstrates higher efficacy. Seroconversion, seroprotection rates, and fold increase in GMT offer limited but valuable insights into vaccine performance. Annual vaccination is crucial for controlling both similar and dissimilar influenza strains.
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)