Original Investigation 

Durability of Respiratory Syncytial Virus Vaccine Effectiveness Among US Veterans

Kristina L. Bajema, David P. Bui, Lei Yan, et al

JAMA Intern Med Published Online: November 24, 2025

doi: 10.1001/jamainternmed.2025.6355

Key Points

Question  What is the long-term effectiveness of a single respiratory syncytial virus (RSV) vaccine dose against RSV illness and associated health care use?

Findings  In a target trial emulation cohort study of 288 111 US veterans who received RSV vaccination between September 2023 and March 2024 and were followed up through March 2025, vaccine effectiveness against documented RSV infections declined from 83% at 0 to 1 month to 59% at 0 to 18 months in the overall cohort and 75% to 40% among immunocompromised persons.

Meaning  The study results suggest that RSV vaccines are effective but that protection declines over time, most notably among immunocompromised individuals.

Abstract

Importance  A single respiratory syncytial virus (RSV) vaccine dose is recommended for older adults and persons at increased risk for severe RSV. Clinical information on the long-term effectiveness of RSV vaccines is needed.

Objective  To determine the effectiveness of RSV vaccination over 2 respiratory illness seasons.

Design, Setting, and Participants  This target trial emulation used data from the Veterans Health Administration and included veterans 60 years and older who were eligible for RSV vaccination from September 2023 to March 2024.

Exposure  A single dose of a recombinant stabilized prefusion F protein RSV vaccine vs no RSV vaccination.

Main Outcomes and Measures  Eligible vaccine recipients were matched with up to 4 unvaccinated individuals in 7 monthly, nested sequential trials from September 1, 2023, to March 31, 2024. Outcomes were ascertained through March 31, 2025. The primary outcome was any positive RSV test result from day 14 following the matched index date. Secondary outcomes included RSV-associated emergency department or urgent care visits, hospitalizations, or intensive care unit admissions. Vaccine effectiveness was estimated as 100 × (1 – risk ratio).

Results  A total of 288 111 vaccinated individuals were matched to 1 075 893 unique control individuals, weighted equally to represent 576 222 individuals, and followed up for a median of 15.8 months (IQR, 14.5-17.0). Across both groups, 544 364 of 576 222 veterans (94.5%) were male, and the median age was 76.1 years (IQR, 71.6-80.0). Vaccine effectiveness against documented RSV infections decreased from 82.5% (95% CI, 77.5%-86.9%) over 0 to 1 month to 59.4% (95% CI, 55.6%-63.5%) over 0 to 18 months of follow-up. During the same period, effectiveness decreased from 84.9% (95% CI, 78.4%-90.2%) to 60.5% (95% CI, 56.4%-65.7%) for emergency visits and 88.9% (95% CI, 77.9%-95.7%) to 57.3% (95% CI, 47.3%-66.4%) for hospitalizations and was 92.5% (95% CI, 61.1%-100.0%) and 71.9% (95% CI, 42.8%-90.0%) for intensive care unit admissions. Among immunocompromised individuals, protection against documented infections decreased from 75.2% (95% CI, 52.5%-89.3%) to 39.7% (95% CI, 23.9%-52.7%).

Conclusions and Relevance  The study found that RSV vaccination was effective in preventing RSV illness and associated health care use but that protection decreased over 2 seasons. Reductions were most notable among immunocompromised persons, suggesting the need to review whether additional vaccine doses may benefit certain risk groups.