Efficacy of Respiratory Syncytial Virus Vaccination to Prevent Lower Respiratory Tract Illness in Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

A systematic review and meta-analysis was designed in order to ascertain the effectiveness of respiratory syncytial virus (RSV) vaccination in preventing lower respiratory tract diseases (LRTD) in older adults (age >= 60 years). Studies reporting on randomized controlled trials (RCTs) were searched for in three databases (PubMed, Embase, and Scopus) and the preprint repository medRxiv until 31 March 2024. A total of nine studies were eventually included, two of which were conference proceedings. Our analysis included five RCTs on five RSV vaccines (RSVpreF, RSVPreF3, Ad26.RSV.preF, MEDI7510, and mRNA-1345). The meta-analysis documented a pooled vaccine efficacy of 81.38% (95% confidence interval (95% CI) 70.94 to 88.06) for prevention of LRTD with three or more signs/symptoms during the first RSV season after the delivery of the vaccine. Follow-up data were available for RSVPreF3 (2 RSV seasons), RSVpreF (mid-term estimates of second RSV season), and mRNA-1345 (12 months after the delivery of the primer), with a pooled VE of 61.15% (95% CI 45.29 to 72.40). After the first season, the overall risk for developing RSV-related LRTD was therefore substantially increased (risk ratio (RR) 4.326, 95% CI 2.415; 7.748). However, all estimates were affected by substantial heterogeneity, as suggested by the 95% CI of I2 statistics, which could be explained by inconsistencies in the design of the parent studies, particularly when dealing with case definition. In conclusion, adult RSV vaccination was quite effective in preventing LRTD in older adults, but the overall efficacy rapidly decreased in the second season after the delivery of the vaccine. Because of the heterogenous design of the parent studies, further analyses are required before tailoring specific public health interventions.