Two new real-world studies estimate the effectiveness of a single dose of a respiratory syncytial virus (RSV) vaccine against hospitalization among older adults at 83% in Denmark and 58% in the United States, respectively.
83% effectiveness among Danish adults
The first study, a phase 4 randomized, controlled, open-label trial, finds an 83% effectiveness for the bivalent (two-strain) RSV prefusion F protein-based (RSVpreF; Abrysvo) vaccine in Danish adults aged 60 years and older.
For the trial, published in the New England Journal of Medicine, a Copenhagen University Hospital–led research team randomly assigned 131,276 participants in a 1:1 ratio to receive RSVpreF vaccine or no vaccine during the 2024-25 respiratory virus season.
The researchers analyzed baseline and outcome data from electronic health records and national registries to determine rates of hospitalization for RSV-related respiratory tract disease and, secondarily, hospitalization for RSV lower respiratory tract disease and for all-cause respiratory tract disease from 14 days post-vaccination to May 31, 2025.
“Phase 3 trials of RSVpreF vaccines against RSV-related lower respiratory tract disease have shown vaccine efficacy levels of 88.9%, 82.6%, and 83.7% for nonadjuvanted, adjuvanted, and mRNA-based forms, respectively,” the study authors wrote. “However, the trials were not designed or powered to evaluate severe outcomes such as hospitalization.” An adjuvant is an immune-enhancing addition.
Study authors included representatives from RSVpreF manufacturer Pfizer, who participated in the trial design and development of the protocol and statistical methods but not in the conduct of the trial or in data collection or analysis.
Statistical success criterion met
During follow-up, 2,236 RSV tests were performed in 2,175 participants (1.7%), including 1,089 participants (1.7%) of RSVpreF recipients and 1,086 (1.7%) in the control group, and 6,660 influenza tests were performed. Of 619 participants hospitalized for any respiratory disease, 22.8% underwent RSV testing—65 of 284 participants (22.9%) in the RSVpreF group and 76 of 335 participants (22.7%) among controls.
Hospitalization for RSV respiratory tract disease occurred in 3 of 65,642 RSVpreF participants and 18 of 65,634 unvaccinated controls (0.11 events vs 0.66 events per 1,000 participant-years; vaccine effectiveness [VE], 83.3%). This finding met the criterion for statistical success of the vaccine (minimum effectiveness of greater than 20%).
Approximately 416,500 to 655,500 of these events could be prevented with the RSVpreF vaccine if the vaccine effectiveness was identical in all populations.
RSVpreF recipients also had fewer hospitalizations for RSV lower respiratory tract disease than controls (1 vs 12; VE, 91.7%) and for all-cause respiratory tract disease (284 vs 335; VE, 15.2%). At least one serious adverse event (SAE) occurred in 3,010 participants—1,341 in RSVpreF recipients and 1,669 in controls during the 6-week safety surveillance period.
An SAE considered related to RSVpreF occurred in five participants. Of these events, two were expected side effects (two cases of headache or malaise), and three were unexpected (one case each of Bell’s palsy, abdominal pain with elevated liver enzymes, and pericarditis, or inflammation of the membrane surrounding the heart).
A total of 50 fatal SAEs occurred (17 in the RSVpreF group and 33 in controls), but none were considered related to the vaccine. By the end of the first season of follow-up, 146 fatal events had occurred in RSVpreF recipients, and 120 had occurred in controls; the between-group difference was not statistically significant.
“An estimated 470,000 to 787,000 RSV-related hospitalizations occur annually among older adults in industrialized nations, and with the estimated vaccine effectiveness observed in this trial, approximately 416,500 to 655,500 of these events could be prevented with the RSVpreF vaccine if the vaccine effectiveness was identical in all populations,” the authors wrote. “Moreover, the true burden of RSV is probably underestimated, in part because of limited testing.”
Significantly lower VE in immune-compromised adults
The second study, which also aimed to determine RSV hospitalization rates among adult patients aged 60 years and older, was published in JAMA.
Researchers with the US Centers for Disease Control and Prevention (CDC) led the multicenter, test-negative, case-control study of 6,958 adult RSV patients hospitalized for acute respiratory illness at 1 of 26 centers in 20 US states from October 2023 to March 2024 or October 2024 to April 2025 and tested within 10 days of illness onset.
Case-patients (821) tested positive for RSV only, while controls (6,137) tested negative for RSV, SARS-CoV-2, and flu. The median participant age was 72 years, 50.8% were women, 62.0% were White, 20.1% were Black, and 26.3% had weakened immune systems. In total, 63 case-patients (7.7%) and 966 controls (15.7%) were vaccinated against RSV.
The researchers obtained demographic and clinical data from patient interviews and electronic health records, estimating a 58% VE a median of 233 post-vaccination during two respiratory virus seasons, regardless of RSV subtype. VE was 69% when vaccination occurred in the same season before symptom onset and 48% when it occurred the previous season, but these estimates weren’t significantly different.
One dose is recommended for all adults aged 75 years or older and those aged 60 to 74 years at increased risk of severe RSV; however, duration of protection is unknown.
The vaccine was 46% effective in adults aged 60 to 74 years and 68% among those aged 75 or older. Protection against poor in-hospital outcomes was maintained over 2 years, with a VE against invasive mechanical ventilation or death of 72%.
A sensitivity analysis limited to adults with healthy immune systems found no VE difference between adults aged 60 to 74 years (67%) and older patients (68%). VE was significantly lower among immune-compromised adults (30%) than among adults with healthy immune systems (67%) in both seasons and among those with cardiovascular disease (56%) versus those without (80%).
RSV vaccines for adults aged 60 years and older became available in the United States in 2023. “One dose is recommended for all adults aged 75 years or older and those aged 60 to 74 years at increased risk of severe RSV; however, duration of protection is unknown,” the investigators wrote, adding that the CDC’s Advisory Committee on Immunization Practices expanded RSV vaccination to adults aged 50 to 59 years at elevated risk of severe RSV.
Need to determine revaccination intervals
Risk factors for RSV hospitalization despite vaccinated status were having a higher median Charlson Comorbidity Index score (meaning having underlying medical conditions) and a greater proportion of moderate or severe immune-compromising conditions (44.4% vs 22.2%).
In addition to Abrysvo, Arexy (made by GSK) and mRESVIA (Moderna) have also been recommended for use in older adults. The first two are protein-subunit vaccines recommended in June 2023, and the latter is an mRNA vaccine recommended in June 2024. In this study, of the 953 vaccinated patients with known vaccine-manufacturer, 55.5% received Arexvy, 44.2% received Abrysvo, and 0.3% received mRESVIA.
Early findings suggest certain subpopulations, including adults with immunocompromise and those with cardiovascular disease, may require additional doses of RSV vaccine earlier than those without these conditions.
“The findings of effectiveness of RSV vaccines during 2 seasons are consistent with findings from prelicensure RSV vaccine trials,” the authors wrote. “However, early findings suggest certain subpopulations, including adults with immunocompromise and those with cardiovascular disease, may require additional doses of RSV vaccine earlier than those without these conditions.”
“As RSV vaccine policy for adults evolves, ongoing monitoring of RSV VE during subsequent seasons is needed to more fully characterize waning of protection and to inform revaccination intervals,” they concluded.
In 2024, the study group published a study on the VE of RSV vaccines against related hospitalization during the first season of use (2023 to 2024) in a diverse population in which nearly a quarter of patients had moderately or severely weakened immune systems.