A single dose of respiratory syncytial virus (RSV) vaccine provides protection against RSV-associated hospitalization and critical illness in adults aged 60 years and older for two consecutive seasons, according to a new study from the IVY Network research group. The findings, published in JAMA, showed that the vaccination reduced the incidence of RSV-associated hospitalization by 58% combined over both seasons.

“These results clearly demonstrate that the RSV vaccines prevent hospitalizations and critical illness due to RSV infection among older Americans,” said Wesley Self, MD, principal investigator for the IVY Network and senior vice president for clinical research at Vanderbilt University Medical Center. “It is exciting to see the public health benefits of this new vaccination program.”

RSV contributes substantially to hospitalizations in the U.S. It is estimated to be responsible for between 100,000 and 150,000 hospitalizations and 4,000 to 8,000 deaths annually of people 60 and older. Since revaccination intervals are still undefined for RSV, the IVY Network’s research sought to evaluate how long protection lasts from a single dose of RSV vaccine.

For this test-negative, case-control study, the investigators used data from 6,958 adults, aged 60 and older, who were hospitalized with acute respiratory illness in 26 hospitals across 20 U.S. states during the 2023–2024 and 2024–2025 RSV seasons. The data showed that vaccine effectiveness (VE) was 69% in the first season and 48% in the second season.

“Our data show that the beneficial effects of RSV vaccines appear to wane over time,” said Self. “Redosing the vaccine at some interval after the initial dose could be a strategy to maintain protection over longer periods of time. It will be important to continue to closely monitor vaccine effectiveness over time to understand how long the benefit lasts after a single dose and if repeat dosing should be considered.”

Three vaccines targeting the RSV prefusion F protein are currently approved for use: Arexvy from GSK, Abrysvo from Pfizer, and mRESVIA from Moderna. Arexvy and mRESVIA are monovalent vaccines targeting RSV subtype A, while Abrysvo is bivalent, covering both subtypes A and B. Current guidelines recommends RSV vaccination for all adults aged 75 years and older, and for those 60 to 74 years old deemed to have elevated risk.

The study’s findings corroborate prelicensure clinical trials, which showed protection from RSV-associated lower respiratory tract disease lasting two to three seasons. However, the real-world VE estimate of 58% is somewhat lower than the 61–81% range seen in clinical trials. The authors attribute this to inclusion of immunocompromised patients and those with cardiovascular disease, who had much lower VE.

The research established that the effectiveness between Arexvy and Abrysvo was comparable, despite differences in valency. However, study could not assess mRESVIA due to low uptake, a data gap that prevented characterization of its clinical performance.

Not surprisingly, the VE among patients with moderate to severe immunocompromise was significantly reduced.

“Adults with immunocompromising conditions or receipt of immunomodulatory agents may be less likely to mount adequate immune responses to RSV vaccination,” the researchers wrote. Immunogenicity studies by GSK and Pfizer have shown that solid organ transplant recipients generate lower neutralizing antibody titers. Similarly, VE during two seasons was lower in patients with cardiovascular disease. “The proinflammatory state present in patients with heart disease may diminish immune responses and contribute both to increased susceptibility to RSV infection and potentially inhibited immune responses after vaccination,” the researchers wrote.

Immunogenicity data have suggested revaccination intervals ranging from 12 to 36 months can boost antibody titers, but not to the same levels observed after the first vaccine. A recent clinical trial showed that revaccination with Arexvy at 12 months did not confer added protection compared to no revaccination.

Limitations of the study noted by the authors include low vaccination rates in the control arm (15.7%). In addition, early adopters may differ in unmeasured ways from the general population, and the study did not account for prior RSV infection. The sample size was also insufficient to stratify VE by types of immunosuppression or duration since vaccination in certain high-risk subgroups.

Plans call for the IVY Network to continue collecting data on vaccine performance across multiple seasons and among different population subgroups to further refine optimal re-dosing intervals.

The IVY (Influenza and Other Viruses in the Acutely Ill) Network is a collaboration of 21 academic medical centers in the U.S. and the Centers for Disease Control and Prevention (CDC) coordinated by Vanderbilt University Medical Center. Founded in 2019, the Network’s mission is to study the epidemiology of severe illness caused by respiratory viruses among adults in the U.S. and the effectiveness of vaccines to prevent those illnesses. Its formation the year before the COVID-19 outbreak proved fortuitous as it contributed important research of COVID-19 vaccines, provided one of the first descriptions of Long COVID, and studied the effectiveness of mRNA COVID-19 vaccines for attenuating illness severity among adults who develop COVID-19 despite vaccination. Member centers include Johns Hopkins Medicine, the Cleveland Clinic, Intermountain Healthcare, and Stanford University, among others.