Long-Term Effectiveness of RSV Vaccine Declines Over Two Seasons, VHA Study Finds

Key Clinical Summary

• Vaccine durability: Effectiveness of a single respiratory syncytial virus (RSV) vaccine dose declined from 83% at 1 month to 59% at 18 months among older US veterans.
• High-risk patients: Immunocompromised individuals saw a sharper drop, from 75% to 40% protection.
• Clinical impact: Findings suggest strong initial protection but waning immunity, supporting consideration of booster strategies.

A new study published by the US Veterans Health Administration (VHA) evaluated the long-term effectiveness of a single dose of the RSV vaccines RSVPreF3 or RSVpreF among older adults. Using real-world data from September 2023 through March 2025, researchers found that vaccine effectiveness (VE) against RSV infection and related health care use declined significantly over 18 months, particularly in immunocompromised populations.

Study Findings

In this target trial emulation cohort study, researchers analyzed data from 288 111 vaccinated US veterans aged 60 years and older, matched with more than 1 million unvaccinated controls across 7 monthly sequential trials. Participants were followed for a median of 15.8 months.

At 1 month post-vaccination, VE against documented RSV infection was 82.5% (95% CI, 77.5% to 86.9%), declining to 59.4% (95% CI, 55.6% to 63.5%) by 18 months. Protection against RSV-associated emergency department (ED) visits dropped from 84.9% to 60.5%, hospitalizations from 88.9% to 57.3%, and intensive care unit (ICU) admissions from 92.5% to 71.9% over the same period.

Among immunocompromised veterans, VE against infection decreased from 75.2% (95% CI, 52.5% to 89.3%) to 39.7% (95% CI, 23.9% to 52.7%), highlighting a marked reduction in long-term protection.

The authors emphasized the study’s strengths, including its large sample size and comprehensive electronic health records within the VHA system, which allowed precise tracking of outcomes across two respiratory illness seasons.

Clinical Implications

These findings underscore that while current RSV vaccines remain effective, protection wanes over time, particularly for immunocompromised and older adults, key populations recommended for vaccination.

For pharmacists and other clinicians, the results suggest a need to monitor patients closely beyond the first RSV season and to consider potential revaccination strategies or booster dose studies to maintain adequate immunity.

As RSV remains a leading cause of severe respiratory illness and hospitalization in adults over 60, understanding the vaccine’s durability is critical for optimizing immunization schedules and counseling patients on ongoing risk.

Conclusion

The VHA study demonstrates that RSV vaccines provide strong short-term protection against infection and hospitalization but wane over 18 months, especially among vulnerable groups. Ongoing surveillance and further research are warranted to assess whether booster dosing could sustain protection across multiple respiratory seasons.

Reference

Bajema KL, Bui DP, Yan L, et al. Durability of respiratory syncytial virus vaccine effectiveness among US veterans. JAMA Intern Med. 2025. doi:10.1001/jamainternmed.2025.6355