Efficacy, Comparative Effectiveness, and Harm of Respiratory Syncytial Virus Vaccines in Adults Who Are Not Pregnant or Immunocompromised: A Rapid Review for the American College of Physicians

BACKGROUND: Respiratory syncytial virus (RSV) causes respiratory disease with a high disease burden in older adults and people with comorbid conditions. PURPOSE: To analyze the efficacy, comparative effectiveness, and harm of RSV vaccines in nonpregnant adults who are not immunocompromised. DATA SOURCES: Ovid Medline, Embase, and ClinicalTrials.gov between January 2023 and October 2025; a recently published Cochrane review to identify studies published before 2023. STUDY SELECTION: Two independent reviewers screened all references on the abstract and full-text levels. DATA EXTRACTION: Two independent reviewers assessed the risk of bias (RoB). One reviewer extracted data and assessed the certainty of evidence (CoE); a second reviewer verified extractions and assessments. For studies carried forward from the Cochrane review, reported data and RoB assessments were used. DATA SYNTHESIS: The review included 7 randomized controlled trials and 1 nonrandomized study. In older adults (≥60 years), RSV protein subunit vaccines probably reduce RSV-related hospitalizations (vaccine efficacy [VE], 83.3% [95% CI, 42.9% to 96.9%]; moderate CoE) and severe RSV illness (VE, 94.1% [CI, 62.4% to 99.9%]; moderate CoE) but have no effect on all-cause mortality (risk ratio [RR], 1.07 [CI, 0.68 to 1.68]; high CoE). They probably do not differ from placebo or no vaccination in serious adverse events (SAEs) (RR, 0.96 [CI, 0.75 to 1.23]; moderate CoE). Messenger RNA (mRNA) vaccines for RSV showed no difference in the incidence of SAEs compared with placebo in older adults (RR, 1.09 [CI, 0.83 to 1.45]; high CoE). LIMITATION: Evidence on RSV vaccines in younger adults and on the efficacy of mRNA vaccines remains insufficient. CONCLUSION: Protein subunit vaccines for RSV decrease the risk for hospitalization and severe illness in older adults. PRIMARY FUNDING SOURCE: American College of Physicians. (PROSPERO: CRD420251145237).