New real-world data confirm that the respiratory syncytial virus (RSV) vaccine offers significant protection for older adults across two consecutive winters. However, the study also highlights weaker responses in individuals with compromised immunity and cardiovascular disease.
A large-scale multicenter study published in JAMA revealed that a single dose of the RSV vaccine is 58% effective in preventing RSV-related hospitalization among older adults during two viral seasons. This finding underscores the vaccine’s potential in reducing the burden of severe RSV infections in this vulnerable population.
Understanding RSV and Its Impact
Respiratory syncytial virus (RSV) is a seasonally prevalent virus in the United States, causing annual epidemics in the fall and winter. The virus can induce severe respiratory illness and chronic cardiorespiratory conditions, particularly in older adults. Annually, an estimated 100,000 to 150,000 RSV-related hospitalizations and 4,000 to 8,000 deaths occur among adults aged 60 years or above in the United States.
To combat this, three RSV vaccines, including two protein-based and one mRNA-based, have been approved and recommended for older adults to prevent severe respiratory illness. In June 2023, a single dose of the RSV vaccine was initially recommended for adults aged 60 years and above. This recommendation was later updated in June 2024 to include all adults aged 75 years or older and at-risk adults aged 60 to 74 years, and again in April 2025 for adults aged 50 to 59 at higher risk of severe RSV infection.
Study Design and Key Findings
The Investigating Respiratory Viruses in the Acutely Ill (IVY) Network, a multicenter surveillance network, conducted the study to assess the vaccine’s effectiveness against hospitalization during two viral seasons among older adults at higher risk of severe RSV infections.
The study population included 6,958 adults aged 60 years or above who were hospitalized with acute respiratory illness during two RSV seasons: from October 1, 2023, to March 31, 2024, and from October 1, 2024, to April 30, 2025. Among the participants, 821 (11.8%) were cases (infected only with RSV), while 6,137 (88.2%) were controls (tested negative for RSV, SARS-CoV-2, and influenza).
The effectiveness of RSV vaccination in preventing RSV-related hospitalization was assessed in the entire study population and was stratified by the interval between vaccine receipt and illness onset.
According to the study estimates, a single dose of the RSV vaccine is 58% effective in preventing RSV-related hospitalization among adults aged 60 years or above during two viral seasons compared to no vaccination. The protection against severe outcomes among hospitalized patients was sustained for two years, with a 72% vaccine effectiveness against invasive mechanical ventilation or death.
Challenges in At-Risk Populations
The study also highlighted challenges in vaccine effectiveness among certain subpopulations. The estimated vaccine effectiveness was 30% among immunocompromised adults, significantly lower than that among immunocompetent adults (67%). A similar reduction in vaccine effectiveness was observed among immunocompetent adults with cardiovascular disease (56%) compared to those without cardiovascular disease (80%).
The effectiveness of the vaccines Arexvy (GSK) and Abrysvo (Pfizer) was similar, and both were effective against RSV A and RSV B subtypes.
Implications and Future Directions
The study highlights the protective efficacy of a single-dose RSV vaccination against RSV-related hospitalization and severe in-hospital outcomes among older adults during two viral seasons. However, the observed reduction in vaccine effectiveness in at-risk subpopulations indicates that older adults with moderate to severe immunocompromising conditions may have lower initial and less durable immune responses to RSV vaccination. This suggests a need for a shorter revaccination interval.
Among older adults with cardiovascular disease, the observed reduction in vaccine effectiveness may be associated with the pro-inflammatory state that diminishes immune responses, contributing to increased susceptibility to RSV infection and potentially inhibiting immune responses after vaccination. Reduced vaccine effectiveness in this subpopulation also highlights the need for a shorter revaccination interval than that for the general older adult population.
Existing evidence on RSV vaccine-specific immune responses suggests that revaccination at intervals ranging from 12 to 36 months after the primary vaccination can boost antibody titers, but not to the same level as after the primary dose. These findings align with the results of a clinical efficacy trial, which demonstrates that older adults reimmunized with the RSV vaccine 12 months after the primary vaccination do not gain additional protection against RSV-related lower respiratory tract disease compared to no revaccination.
The Advisory Committee on Immunization Practices has recently expanded RSV vaccination to adults aged 50 to 59 who are at higher risk of severe RSV infection. Such reformation of vaccine policy for adults highlights the need for continuous monitoring of vaccine efficacy to accurately characterize waning protection and inform revaccination intervals.
