RSV vaccine slashes hospitalizations in older adults in real-world trial

By Hugo Francisco de SouzaReviewed by Susha Cheriyedath, M.Sc.Sep 15 2025

A Danish national registry trial shows the RSVpreF vaccine is highly effective at preventing severe RSV illness and related hospitalizations in older adults, offering real-world support for broader immunization strategies.

Study: RSV Prefusion F Vaccine for Prevention of Hospitalization in Older Adults. Image Credit: CI Photos / Shutterstock

In a recent study published in The New England Journal of Medicine, researchers investigated the efficacy of the novel bivalent RSV prefusion F protein-based vaccine (RSVpreF) in preventing severe symptomatic Respiratory Syncytial Virus (RSV) infections, particularly in older adults (60 years and older).

The study leveraged an extensive (131,000 participants), open-label, pragmatic randomized trial conducted in Denmark during the 2024–2025 winter season. Participants aged 60 and above were primarily recruited via digital invitations through the national registry infrastructure. The trial was designed to reflect real-world conditions, utilizing broad eligibility criteria and integrating administrative health registries for recruitment, randomization (1:1 – vaccine vs. no trial-administered vaccine), and outcome tracking.

Findings revealed that the vaccine was 83.3% effective at preventing rigorously defined RSV-related hospitalizations (based on ICD-10 codes or positive tests within 7 days of admission) and 91.7% effective against RSV-related lower respiratory tract disease hospitalizations, confirming its role in protecting older populations within a real-world trial framework.

Background

Respiratory Syncytial Virus (RSV) is a negative-sense, single-stranded RNA virus that, while common across age groups, can cause severe respiratory illness in infants and older adults, often leading to hospitalization of the latter. Reports highlight an estimated 470,000 hospitalizations and 33,000 deaths in adults aged 60 or more annually in industrialized nations. Despite this burden, routine RSV testing remains limited, potentially underestimating true incidence.

About the Study

Titled A Pragmatic Randomized Trial to Evaluate Bivalent RSV Prefusion F Protein–based Vaccine Effectiveness for Preventing RSV Hospitalizations in Adults Aged 60 Years or Above (DAN-RSV), the trial randomly assigned 131,276 adults in a 1:1 ratio to receive either the RSVpreF vaccine or no trial-administered vaccine (control group). Notably, 1.2% of controls sought RSV vaccination outside the trial. The study's primary endpoint was hospitalization for RSV-related respiratory tract disease, defined using national registry data through ICD-10 codes or a positive RSV test within 7 days before or after admission. Key secondary endpoints included hospitalization for RSV-related lower respiratory tract disease and hospitalization for respiratory tract disease from any cause, tested hierarchically after the primary endpoint.

Study Findings

The study’s findings demonstrated significant efficacy, with only three hospitalizations for RSV-related respiratory tract disease in the 65,642 participants who received the vaccine, compared to 18 hospitalizations in the 65,634 participants in the control group. Fewer events occurred than expected, partly due to reduced RSV testing in Denmark following the COVID-19 pandemic.

These findings translate to a vaccine effectiveness of 83.3% (95% Confidence Interval [CI], 42.9–96.9), exceeding the prespecified success criterion of 20% (p = 0.007). The vaccine also showed benefit against broader outcomes: 91.7% efficacy against RSV-related lower respiratory tract hospitalization (1 vs. 12 events; 95% CI, 43.7–99.8; p=0.009); a 15.2% reduction in any respiratory tract disease hospitalization (284 vs. 335; 95% CI, 0.5–27.9; p=0.04), though this secondary endpoint was not adjusted for multiplicity after hierarchical testing; and a 9.9% reduction in cardiorespiratory hospitalizations (exploratory). The greater absolute reduction in hospitalizations for respiratory disease from any cause (compared to confirmed RSV cases) suggests that the vaccine prevented many hospitalizations where RSV infection went undiagnosed due to limited testing.

The incidence of serious adverse events was similar between the two groups within 6 weeks of vaccination. Five vaccine-related SAEs occurred (including pericarditis and Bell’s palsy), and a non-significant mortality imbalance emerged by season’s end (146 vs. 120 deaths).

Conclusions

The study provides robust evidence from a pragmatic trial that RSVpreF significantly reduces RSV-related hospitalizations in adults aged 60 and older. By leveraging a large-scale, open-label design and national registries, the study addresses limitations of earlier trials. While potential healthy-volunteer bias and undertesting of RSV remain caveats, the vaccine demonstrated protection against severe outcomes with a manageable safety profile.