Effectiveness and Safety of Respiratory Syncytial Virus Vaccine for US Adults Aged 60 Years or Older
Authors: Sarah E. Fry, Pauline Terebuh, David C. Kaelber, Rong Xu, Pamela B. Davis
Journal: JAMA Network Open (2025)

Importance Respiratory syncytial virus (RSV) is associated with hospitalization and death among older adults. Characterizing the safety and effectiveness of recently introduced vaccines against RSV is critical. Objective To assess the safety and effectiveness of vaccines against RSV and the major adverse events among patients aged 60 years or older during the 2023-2024 RSV season. Design, Setting, and Participants In this study using a data platform containing electronic health records for more than 270 million patients across the US, a test-negative case-control design was used to estimate vaccine effectiveness (VE), and a self-controlled case series of vaccine recipients was included to estimate vaccine-associated adverse events. Records from participants aged 60 years or older with acute respiratory infection (ARI) and testing for RSV between October 1, 2023, and April 30, 2024, were included in the VE study. For vaccine safety analysis, all participants aged 60 years or older who received the RSV vaccine from July 1, 2023, to June 30, 2024 were included. Data were analyzed from August 2024 to March 2025. Main Outcomes and Measures Cases were those patients who tested positive for RSV, and controls were those who tested negative for RSV. Patients were classified as vaccinated if the vaccine was received at least 14 days before testing. VE against RSV-associated ARI diagnosis, emergency department or urgent care visits, or hospitalizations was estimated using (1 − odds ratio) × 100%. Excess risks of immune thrombocytopenic purpura and Guillain-Barré syndrome diagnosis for 6 weeks after vaccine administration were calculated. Results Of 787 822 patients tested for RSV, 53 963 were positive (733 859 were controls); 1318 cases (2.4%) and 66 928 controls (9.1%) were vaccinated. Overall, VE was 75.1% (95% CI, 73.6%-76.4%) against ARI and was similar for age groups of 60 to 74 years and 75 years or older and against urgent care visits or hospitalizations. Immunocompromised patients had a VE from 67.0% (95% CI, 62.6%-70.9%) for patients aged 60 to 74 years to 73.1% (95% CI, 69.9%-76.0%) for those aged 75 years or older, and the lowest VE (ie, from 29.4% [95% CI, 3.5%-48.4%] for patients aged 60-74 years to 44.4% [95% CI, 1.0%-68.8%] for those aged ≥75 years) was for a subgroup of patients who received stem cell transplants. Among 4 746 518 vaccine recipients, no excess risk of immune thrombocytopenic purpura diagnosis was detected. An excess of 5.2 cases (RSVPreF3+AS01) or 18.2 cases (RSVPreF) of Guillain-Barré syndrome were diagnosed per 1 000 000 doses of RSV vaccine administered. Conclusions and Relevance VE for the RSV protein subunit vaccine in this case-control study was similar to the VE in clinical trials. The VE for immunocompromised patients was mildly (overall) to moderately (for stem cell transplant recipients) diminished. Risk of immune thrombocytopenic purpura after vaccination was not elevated, but the risk of Guilain-Barré syndrome was statistically significantly elevated in patients who received the RSVPreF vaccine but not in those who received RSVPreF+AS01 vaccine, although the risk was small. These observations should inform clinicians’ choices and patient instructions.