A large case-control study published in JAMA, 787,822 US adults aged 60 and older found that respiratory syncytial virus (RSV) vaccines were 75.1% effectively prevented RSV-associated acute respiratory infections (ARI), including emergency department visits and hospitalizations. The study also identified a small but measurable increase in Guillain-Barré syndrome diagnoses following vaccination.
The vaccine's effectiveness was consistent across age groups 60–74 and 75 and older. Among immunocompromised patients, vaccine effectiveness (VE) ranged from 67.0% to 73.1%. VE dropped to between 29.4% for stem cell transplant recipients and 44.4%.
Safety data from 4,746,518 vaccine recipients showed no excess risk for immune thrombocytopenic purpura. Although, Guillain-Barré syndrome was diagnosed in more than 5.2 cases per 1 million doses for RSVPreF3+AS01 and 18.2 cases per 1 million doses for RSVPreF.
What You Need To Know
The RSV protein subunit vaccine was 75.1% effective in preventing RSV-associated acute respiratory infections and hospitalizations in adults aged 60 and older, with consistent effectiveness across age groups.
There was a small increase in Guillain-Barré syndrome diagnoses, particularly with the RSVPreF formulation, but no excess risk for immune thrombocytopenic purpura.
The ACIP recommended the RSV vaccine for at-risk adults aged 50–59, and real-world data from the JAMA study supports its continued and expanded use in high-risk adults.
In the investigator's discussion, they said, "Our data confirm that, during the first year after licensure, vaccines against RSV based on protein subunits of the virus are effective in persons aged 60 years or older. VE of approximately 75% was similar for both patients aged 60 to 74 years and those aged 75 years or older against all outcomes: ARI-associated encounters overall, ARI-associated emergency or urgent care visits, or ARI-associated hospitalization."
The study used a test-negative case-control design and a self-controlled case series analysis. Data were collected from US electronic health records between October 2023 and April 2024 for vaccine effectiveness and between July 2023 and June 2024 for vaccine safety. Cases included those who tested positive for RSV; controls tested negative. Participants were considered vaccinated if the RSV vaccine was administered at least 14 days before testing.
Researchers concluded that the RSV protein subunit vaccine remains effective in older adults and most immunocompromised patients. Clinicians should consider the small but elevated risk of Guillain-Barré syndrome, particularly with the RSVPreF formulation, when making vaccination decisions.
This study has several limitations. Some vaccinated patients may not have had their vaccination recorded in the EHR, although the impact of this is likely small. Misclassification of vaccinated patients as unvaccinated may have reduced VE estimates. The test-negative case-control design minimizes confounding, but care-seeking behaviors and undiagnosed infections could still affect results. RSV diagnostic tests may lead to misclassification, and the study does not account for all comorbidities. GBS diagnoses may lack full confirmation, and the cause of hospitalization could be influenced by underlying diseases. The data platform used may not be fully representative of the entire US population, and this observational study can only suggest associations, not causation.
At the April 16, 2025, ACIP meeting, the committee recommended a single dose of RSV vaccine for adults aged 50–59 years who are at increased risk of severe RSV disease, expanding current guidance beyond the 60+ age group. The vaccine can be co-administered with other licensed vaccines, and no additional doses are advised for those already vaccinated. ACIP discussed Moderna’s mRNA-1345 and GSK’s Arexvy vaccines, with attention to revaccination intervals and clinical/economic impact. Broader expansion to at-risk adults aged 18–49 is under review, though data are not yet sufficient for a recommendation.2
This guidance aligns with findings from the JAMA study showing that RSV vaccines are approximately 75% effective in adults aged 60+ against RSV-related illness and hospitalization. The study also found that vaccine effectiveness remained substantial among immunocompromised individuals, though slightly reduced. These real-world outcomes support continued and expanded use of RSV vaccines in high-risk adults.
References
1. Fry SE, Terebuh P, Kaelber DC, Xu R, Davis PB. Effectiveness and Safety of Respiratory Syncytial Virus Vaccine for US Adults Aged 60 Years or Older. JAMA Netw Open. 2025;8(5):e258322. doi:10.1001/jamanetworkopen.2025.8322
