Research Summary

Does a Single RSV Vaccine Dose Protect Older Adults Across Multiple Seasons?

Anthony Calabro, MA

Key Highlights

  • Respiratory syncytial virus (RSV) vaccine effectiveness (VE) against hospitalization among adults ≥60 years was 58% across 2 RSV seasons.
  • VE was higher for same-season vaccination (69%) than prior-season vaccination (48%), though not statistically different.
  • VE was significantly lower in immunocompromised adults (30%) and those with cardiovascular disease (56%).

In a multicenter test-negative, case-control study conducted by Diya Surie, MD, and colleagues, one dose of a respiratory syncytial virus (RSV) vaccine reduced the risk of RSV-associated hospitalization among older adults across 2 consecutive seasons. The vaccine’s effectiveness (VE) was moderate overall but varied substantially by patient subgroup and timing since vaccination.

Respiratory syncytial virus is a leading cause of severe respiratory illness and hospitalization in older adults, with annual US estimates of 100,000 to 150,000 hospitalizations and 4000 to 8000 deaths. Vaccines targeting the RSV prefusion F protein became available in 2023, including respiratory syncytial virus vaccine, adjuvanted (recombinant) (Arexvy, GlaxoSmithKline), respiratory syncytial virus vaccine (RSV prefusion F protein) (no adjuvant) (Abrysvo, Pfizer), and respiratory syncytial virus vaccine (mRNA) (mRESVIA, Moderna).

Early recommendations emphasized shared decision-making for adults aged 60 years or older, but uncertainty remained about the duration of protection, particularly for immunocompromised patients and those with chronic cardiopulmonary disease who were underrepresented or excluded in prelicensure trials.

The study enrolled 6958 adults aged ≥ 60 years hospitalized with acute respiratory illness at 26 hospitals in 20 US states during the 2023–2024 and 2024–2025 RSV seasons. Patients were included if they underwent respiratory viral testing within 10 days of illness onset. Case patients tested positive for RSV only, while controls tested negative for RSV, SARS-CoV-2, and influenza. Vaccination status was verified via medical records, registries, and interviews. Vaccine effectiveness against RSV hospitalization was estimated using multivariable logistic regression, adjusting for demographics, region, and seasonality. Analyses also stratified by vaccination timing (same vs prior season), age, immunosuppression, and comorbidities.

Of the 6958 patients, 821 (11.8%) were RSV-positive cases and 6137 (88.2%) controls. Median age was 72 years, and 26.3% were immunocompromised. Overall, 58% VE (95% CI, 45%-68%) was observed across 2 seasons. VE was higher when vaccination occurred in the same season before illness onset (69%) compared with the prior season (48%), although the difference was not statistically significant.

Subgroup analyses showed that VE was markedly lower in immunocompromised adults (30%) compared with immunocompetent adults (67%, P = .02) and in patients with cardiovascular disease (56%) compared with those without (80%, P = .03). VE did not differ significantly between Arexvy and Abrysvo or between RSV subtypes A and B. Protection against severe outcomes was notable, with VE of 73% against acute respiratory failure, 73% against acute organ failure, 67% against intensive care unit admission, and 72% against mechanical ventilation or death.

This study had limitations, including a relatively low proportion of vaccinated controls, which may reflect early-adopter bias and residual confounding, as well as insufficient sample sizes for detailed subgroup analyses by immunosuppression type or vaccine product. The study also did not account for prior RSV infection, which may influence hospitalization risk independent of vaccination.

“Respiratory syncytial virus vaccines prevented RSV-associated hospitalization during 2 seasons, although effectiveness was lower in patients with immunocompromise and cardiovascular disease than in those without these conditions,” Surie and colleagues concluded. “Ongoing monitoring is needed to determine the optimal RSV revaccination interval.”

Reference
Surie D, Self WH, Yuengling KA, et al. RSV vaccine effectiveness against hospitalization among us adults aged 60 years or older during 2 seasons. JAMA. Published online August 30, 2025. doi:10.1001/jama.2025.15896