7 6 potential manufacturing advantages that facilitate quick adaptation to antigenic changes. A comprehensive review published in Cureus noted that mRNA-based vaccines, alongside protein- subunit and viral vector platforms, have collectively demonstrated effectiveness in reducing hospital admissions and the risk of LRTD from RSV.1 The researchers highlighted that each platform offers distinct immunogenic properties and safety profiles, and that ongoing pharmacovigilance remains critical to detecting rare adverse events. Protection Wanes Over Two Seasons While all three approved vaccines have demonstrated real-world effectiveness, a large veteran-focused study published in JAMA Internal Medicine earlier this year shed light on the duration of that protection.2 Researchers led by Kristina Bajema, MD, of the VA Portland, OR, Healthcare System and Oregon Health and Science University led a target trial emulation cohort study involving 288,111 U.S. veterans aged 60 years and older who received RSV vaccination between September 2023 and March 2024. The study followed the veterans through March 2025, spanning two full respiratory illness seasons in one of the most comprehensive real-world durability assessments of RSV vaccines conducted to date. The investigators, which included researchers from the VA Cooperative Studies Program Clinical Epidemiology Research Center at the VA Connecticut Health Care System and VA Puget Sound Health Care System, matched vaccinated individuals to more than one million unique unvaccinated controls. They weighted the groups to represent 576,222 individuals in a cohort was 94.5% male with a median age of 76.1 years, reflecting the veteran population’s demographic profile. Across both seasons, vaccine effectiveness against documented RSV infections declined from 82.5% during the first one to two months after vaccination to 59.4% over the full 18-month follow-up period. Protection against RSV-associated emergency department and urgent care visits followed a similar trajectory, falling from 84.9% early to 60.5% over 18 months. Effectiveness against hospitalizations dropped from 88.9% to 57.3% while intensive care unit admissions declined from 92.5% to 71.9%. While still providing a meaningful reduction in risk, the data clearly showed protection waned considerably over the study period compared to that observed in the first months post-vaccination. “The study results suggest that RSV vaccines are effective, but that protection declines over time, most notably among immunocompromised individuals,” the lead investigators wrote. Immunocompromised veterans saw protection against documented RSV infection fall from 75.2% in early follow-up to 39.7% over 18 months, a steeper decline than observed in the overall cohort in a this distinctly more vulnerable population. The study did not include mRNA-based vaccines, but a 2022 study in Cytokine & Growth Factor Reviews explained how different those are than traditional vaccines based on live or inactivated attenuated virus, or subunit proteins derived from the pathogens.3 “Although these vaccines produce an effective immune response, they have a number of associated safety concerns,” the authors explained. “Meanwhile, nucleic acid-based vaccines have the potential to offer the combined safety and efficacy of live attenuated and subunit vaccines. While DNA vaccines can induce simultaneous humoral immunity and cellular immune responses, their protection efficiency is typically low, and nucleic acid may integrate into the host genes . Alternatively, mRNA vaccines are safer and simpler as they do not pose a risk of nucleic acid integration into the host genome and can be naturally degraded in vivo, thus, having a wide application prospect.” Older and Immunocompromised Veterans At Greatest Risk The findings regarding immunocompromised individ- uals and adults 80 years and older are particularly rel- evant for VA clinicians, as these groups were largely excluded from or underrepresented in the original RSV vaccine clinical trials. Among veterans 80 years and older, vaccine effec- tiveness over the full follow-up period was approxi- mately 50%, lower than the overall cohort, though still clinically meaningful. Immunocompromised vet- erans in this age group fared less well, with effective- ness approaching 40% by the end of two seasons. The researchers pointed out that clinical trials were lim- ited by low enrollment of participants 80 and older, exclusion of immunocompromised individuals, and a lower prevalence of cardiopulmonary and other medi- cal conditions than found in real-world populations, particularly at the VA. “At present, to our knowledge, there is no recommendation for additional vaccine doses,” the
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