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Bivalent RSV Prefusion F Vaccine to Prevent Hospitalizations in Adults
Tor Biering-SørensenMats C. LassenSine H. ChristensenMarat YafasovManan PareekNiklas Dyrby JohansenAbby E. RudolphCarmen R-T. SánchezKristoffer Grundtvig SkaarupDaniel ModinBrian L. ClaggettCarsten S. LarsenLykke LarsenLothar WieseMichael Dalager-PedersenMatias G. LindholmAnne Marie R. JensenMaria DonsK Feldballe BernholmFilip S. DavidovskiLisa Steen DuusCamilla I. OttosenAnne B. NielsenJulie H. BorchseniusCaroline EspersenGüldas KöseFrederik H. FussingIngrid T. LenzJacob ChristensenJakob Ø. SimonsenMajid AfzalKatja V. BartholdyAdam C. F. LanghoffLars KøberScott D. SolomonJens Ulrik Stæhr JensenCyril Jean-Marie MartelIago Giné-VázquezCarmen Duran-ParrondoMarta Piñeiro-SoteloMartín Cribeiro-GonzálezMónica Conde-PájaroSusana Mirás-CarballalJuan-Manuel González-PérezBradford D. GessnerNegar AliabadiClaudia SchwarzMette SkovdalLawrence H. MoultonPingping ZhangV. López-GómezSabrina WelshLaura Anatale‐TardiffAlejandro CaneKyla HayfordFederico Martinón-TorresElizabeth Begier
Key result
RSVpreF cuts RSV-related respiratory hospitalizations ~70% versus no vaccine in expanded ESC 2026 follow-up.
- vaccine effectiveness 70.3%
- 95% CI 49.7-83.2
- n=513,358
Why the trial?
RSV infection in older adults triggers both respiratory and cardiovascular hospitalisations, but whether RSV vaccination prevents these cardiorespiratory events had not been demonstrated in a randomised trial powered for clinical outcomes.
Does the bivalent RSV prefusion F vaccine reduce RSV-related respiratory tract disease hospitalization in adults?
Key Points
- To assess the efficacy and safety of the bivalent RSV prefusion F (RSVpreF) vaccine in preventing RSV-related hospitalizations among adults.
- Pragmatic, open-label, randomized trial (NCT06684743) conducted in Denmark and Spain across the 2024–2025 and 2025–2026 winter seasons.
- A total of 513,358 adults (initially ≥60 years old in Denmark, expanded to ≥18 years old in Denmark and Spain) were randomly assigned in a 1:1 ratio to receive RSVpreF or no vaccine.
- The primary endpoint was RSV-related respiratory tract disease (RTD) hospitalization in the intention-to-treat population, with secondary endpoints evaluating RSV-related lower RTD and all-cause RTD hospitalizations.
- RSV-related RTD hospitalization occurred at 0.16 events per 1000 person-years in the RSVpreF group compared to 0.55 per 1000 person-years in the control group, representing a vaccine effectiveness of 70.3% (95% CI, 49.7–83.2).
- Incidence of RSV-related lower RTD hospitalization was 0.11 versus 0.39 events per 1000 person-years, reflecting a vaccine effectiveness of 71.1% (95% CI, 45.4–85.7), whereas all-cause RTD hospitalization was 11.16 versus 12.01 per 1000 person-years with a vaccine effectiveness of 7.1% (95% CI, -0.3–13.9).
- Serious adverse events occurred at similar rates across trial arms, affecting 2.0% of participants in the RSVpreF group and 2.2% in the no-vaccine group.
Evidence details
What drove the result?
| Outcome | RSVpreF | No vaccine |
|---|---|---|
| RSV respiratory hospitalization, adults >=60 (2025 primary) | 0.11 | 0.66 |
| Per 1000 participant-years; 83.3% vaccine effectiveness (2025 NEJM primary) | ||
| RSV respiratory hospitalization, expanded cohort | 0.16 | 0.55 |
| Per 1000 person-years; ~70% effectiveness in ESC 2026 expanded follow-up incl. broader adult cohort | ||
Limitations & tradeoffs
Design limitations
the ESC 2026 readout is an expanded follow-up without a new results paper; the 2025 NEJM publication remains the primary source.
Statistical certainty
cohort sizes, confidence intervals, and follow-up duration are not reported in the record.
Structured PICO
Does the bivalent RSV prefusion F vaccine reduce RSV-related respiratory tract disease hospitalization in adults?
P
Population
513,358 adults (initially ≥60 years in Denmark, expanded to ≥18 years in Denmark and Spain) randomized to RSVpreF vaccine or no vaccine.
I
Intervention
Bivalent RSV prefusion F (RSVpreF) vaccine
C
Comparator
No vaccine
O
Outcome
RSV-related respiratory tract disease (RTD) hospitalization in the intention-to-treat populationhard clinical
Main Result
Effect estimate: vaccine effectiveness 70.3% (95% CI 49.7-83.2)
Absolute Event Rate: 0.16% vs 0.55%
The bivalent RSV prefusion F vaccine significantly reduces the incidence of RSV-related respiratory tract disease hospitalization in adults compared to no vaccine.
Discussion
Key questions
No takes yet. Share an insight, caveat, or question.
Where experts stand
Experts broadly view DAN-RSV's ~70% vaccine effectiveness against RSV-related hospitalization as compelling real-world evidence, though some flag the very low absolute event rate and an unresolved question about optimal revaccination timing.
Cardiologists and infectious-disease specialists are treating DAN-RSV as strong pragmatic evidence that RSV vaccination protects older adults from hospitalization, with particular relevance for patients with cardiovascular disease. Most reactions are enthusiastic, calling the vaccine an underutilized and affordable prevention strategy, but a minority voice highlights very low absolute event rates and a numerical imbalance in all-cause deaths that merits attention. Open questions center on how long protection lasts and whether revaccination intervals can be defined.
Agreement
Multiple clinicians and investigators agree that RSV vaccination in older adults can reduce not just respiratory but also downstream cardiovascular complications, framing it as a cardiorespiratory prevention strategy.
4 clinicians say this directly
Main debate
Large relative benefit versus very low absolute event rates and an unexplained mortality signal
Striking pragmatic benefit2
A 70% reduction in RSV-related hospitalizations in a half-million-person pragmatic trial is strong real-world evidence for broad vaccination.vs
Low absolute events, mortality question1
With very few RSV events in either group and a non-significant trend toward more deaths among vaccinated participants, the overall benefit may be smaller than the relative numbers suggest.Not placed5 reporting, watching, or context only
3 takes classified by contention axis so far — the map appears as more land.
Still unclear
The optimal revaccination interval remains unknown, as one commentator explicitly noted. Whether the numerical imbalance in all-cause deaths (146 vs 120) warrants concern or is a chance finding in an underpowered comparison has not been resolved. It also remains unclear how RSV vaccination guidelines will evolve for cardiovascular disease patients specifically.
Key expert perspectives
AJACC Journal Scan
“Determining the optimal timing for re-vaccination continues to remain a priority for future research, particularly for higher-risk groups including immunocompromised individuals or those with underlying cardiopulmonary disease. Together, these data provide real-world evidence to support RSV vacci...”
Very low absolute RSV event rates and a numerical mortality signal temper the 71% efficacy headline
Points out that despite 71% efficacy, RSV events were extremely rare in both groups (0.11 vs 0.37 events per 1000 person-years). Notes that all-cause deaths numerically favored the control group (146 vaccinated vs 120 controls), with a risk ratio of 1.22 that just crossed 1.0.
Distilled from their postX post
A striking 70% reduction in a huge pragmatic trial positions RSV vaccination as cardiovascular prevention
Frames RSV as more than a respiratory infection, noting its role in triggering heart failure decompensation and cardiovascular events. Calls the 70.3% vaccine effectiveness across more than 500,000 participants a striking result.
Implication
Supports RSVpreF vaccination in older adults with CVD; extends efficacy data to cardiorespiratory hospitalization prevention.
Abstract
BACKGROUND: Respiratory syncytial virus (RSV) is an important cause of severe respiratory disease in adults, with the highest burden among older adults and individuals with chronic health conditions. The bivalent RSV prefusion F (RSVpreF) vaccine has been shown to prevent RSV-associated respiratory illness, but data from randomized trials regarding its effect on hospitalization outcomes are limited. METHODS: In this pragmatic, individually randomized, open-label trial conducted in Denmark and Spain, adults were assigned in a 1:1 ratio to receive RSVpreF or no vaccine. During the first year of enrollment, participants who were 60 years of age or older in Denmark were enrolled; during the second year, eligibility was expanded to participants 18 years of age or older in Denmark and Spain. The results of the first year of enrollment have been reported previously; because fewer RSV-related hospitalization events than anticipated occurred in the first year, demographic and geographic enrollment was expanded. The primary endpoint was RSV-related respiratory tract disease (RTD) hospitalization in the intention-to-treat population. Secondary endpoints included RSV-related lower RTD and all-cause RTD hospitalization. RESULTS: Of 513,358 participants who underwent random assignment during the 2024-2025 and 2025-2026 winter seasons, the incidence rate of RSV-related RTD hospitalization was 0.16 events per 1000 person-years in the RSVpreF group and 0.55 events per 1000 person-years in the control group, corresponding to an estimated vaccine effectiveness of 70.3% (95% confidence interval [CI], 49.7-83.2). The incidence of RSV-related lower RTD hospitalization was 0.11 and 0.39 events per 1000 person-years in the RSVpreF vaccine and no-vaccine groups, respectively, corresponding to an estimated vaccine effectiveness of 71.1% (95% CI, 45.4-85.7) and the incidence of all-cause RTD hospitalization was 11.16 and 12.01 events per 1000 person-years in the RSVpreF vaccine and no-vaccine groups, respectively, corresponding to an estimated vaccine effectiveness of 7.1% (95% CI, -0.3-13.9). The incidence of serious adverse events was 2.0% in the RSVpreF vaccine group and 2.2% in the no-vaccine group. CONCLUSIONS: In a randomized trial that included expanded demographic and geographic enrollment during a second RSV season, the RSVpreF vaccine was associated with a lower incidence of RSV-related respiratory tract disease hospitalization as compared to no vaccine. (Funded by Pfizer; ClinicalTrials.gov number, NCT06684743.).
Coverage & sources
Journal, society, and media accounts. Useful signal, not independent expert judgment.
Cite This Study
Lassen et al. (2026) conducted an RCT in Respiratory syncytial virus (RSV) respiratory disease (n=513,358). Bivalent RSV prefusion F (RSVpreF) vaccine vs. No vaccine was evaluated on RSV-related respiratory tract disease (RTD) hospitalization in the intention-to-treat population (vaccine effectiveness 70.3%, 95% CI 49.7-83.2). The bivalent RSVpreF vaccine reduced RSV-related respiratory tract disease hospitalization compared to no vaccine (0.16 vs 0.55 events per 1000 person-years; vaccine effectiveness 70.3%).