Research Summary

RSV Prefusion F Vaccine Significantly Reduces RSV-Related Hospitalizations in Older Adults in Denmark

Edited by:
Ashton L. Stahl

Key Highlights:

  • The RSV prefusion F (RSVpreF) vaccine reduced RSV-related respiratory hospitalization by more than 80% compared with no vaccination.
  • Fewer hospitalizations were observed for RSV-related lower respiratory tract disease and for respiratory tract disease from any cause.
  • Serious adverse events occurred at similar rates in vaccinated and unvaccinated groups.

A bivalent respiratory syncytial virus prefusion F protein-based vaccine (RSVpreF) significantly reduced hospitalizations for RSV-related respiratory tract disease in adults aged 60 years or older, according to findings published in The New England Journal of Medicine. The phase 4 DAN-RSV trial was designed to assess real-world vaccine effectiveness against severe RSV outcomes, particularly hospitalization, an endpoint that was not adequately powered in earlier phase 3 trials.


The investigators conducted a pragmatic, open-label, individually randomized trial in Denmark during the 2024-2025 RSV season. Adults aged 60 years or older were randomized 1:1 to receive a single intramuscular dose of the RSVpreF vaccine or no RSV vaccine. Baseline characteristics and outcomes were captured through nationwide Danish health registries, with follow-up beginning 14 days after the scheduled trial visit and continuing through May 31, 2025. The primary endpoint was hospitalization for RSV-related respiratory tract disease, with key secondary endpoints, including hospitalization for RSV-related lower respiratory tract disease and hospitalization for respiratory tract disease from any cause.

Study Findings

Among the 131,276 participants included in the intention-to-treat analysis, hospitalization for RSV-related respiratory tract disease occurred in 3 vaccinated participants and 18 control participants. This data corresponded to incidence rates of 0.11 versus 0.66 events per 1,000 participant-years and a vaccine effectiveness of 83.3% (95% CI, 42.9-96.9). Hospitalizations for RSV-related lower respiratory tract disease were also reduced (1 event vs 12 events), yielding a vaccine effectiveness of 91.7% (95% CI, 43.7-99.8). In addition, hospitalizations for respiratory tract disease from any cause were lower in the RSVpreF group than in controls (284 vs 335 events), with a vaccine effectiveness of 15.2% (95% CI, 0.5-27.9).

Clinical Implications

According to the study authors, these findings suggest that RSVpreF vaccination can meaningfully reduce severe RSV outcomes requiring hospitalization in older adults. The results support the vaccine’s role in preventing clinically significant RSV disease during winter seasons and demonstrate effectiveness against hospitalization endpoints in a large, real-world population, while maintaining a safety profile comparable to no vaccination.

Expert Commentary

“In this large-scale, pragmatic, phase 4 trial, the RSVpreF vaccine as compared with no vaccine reduced the incidence of hospitalization for RSV-related respiratory tract disease, as well as the incidence of hospitalization for respiratory tract disease from any cause, among adults 60 years of age or older,” the researchers concluded.

Reference:
Lassen MCH, Johansen ND, Christensen SH, et al. RSV prefusion F vaccine for prevention of hospitalization in older adults. N Engl J Med. 2026;394:138-151. doi:10.1056/NEJMoa2509810