Abstract
BACKGROUND: Although the respiratory syncytial virus (RSV) membrane protein F has become one of the major target proteins for RSV vaccine development, previous studies have identified safety issues with RSV vaccines in older adults. The causes of these issues remain unclear. OBJECTIVE: We aimed to evaluate the safety and efficacy of a novel RSV preF vaccine in preventing lower respiratory tract infections (LRTIs) and RSV-associated acute respiratory illnesses (RSV-ARIs) in older adults. METHODS: We conducted a systematic review of randomized controlled trials from 5 databases-PubMed, Embase, the Cochrane Library, Web of Science, and the Cochrane Central Register of Randomized Controlled Trials-published up to July 31, 2024. For categorical variables, we used the risk ratio; for continuous variables, we used the weighted mean difference or standardized mean difference. We extracted key study characteristics and assessed their quality using the Newcastle-Ottawa Scale. Sensitivity analyses were used to evaluate the impact of individual studies on pooled effects, and publication bias was examined with Egger and Begg tests. RESULTS: Meta-analysis of 5 studies (101,825 older adults) showed a reduced LRTI incidence in the vaccinated group, with heterogeneity resolved after excluding 1 study. Analysis of 4 studies (99,931 participants) confirmed a lower RSV-ARI incidence with no heterogeneity. Safety analysis (14 studies, 76,695 participants) showed higher adverse events (AEs) in the vaccinated group, mainly injection-site reactions and vaccine-related AEs, but no significant difference in serious AEs. Subgroup analyses identified potential sources of AE heterogeneity, and sensitivity analyses confirmed the efficacy but suggested variability in the injection-site reactions. . CONCLUSIONS: This meta-analysis showed a statistically significant difference in the incidence of LRTI and RSV-ARI between the vaccine and placebo groups in older adults. However, no significant differences were observed in overall AEs or serious AEs.