Effectiveness of the mRNA-1345 Vaccine Against Respiratory Syncytial Virus in US Veterans
9 affiliations
- 1Veterans Affairs (VA) Portland Health Care System, Portland, Oregon
- 2VA Cooperative Studies Program Clinical Epidemiology Research Center, VA Connecticut Health Care System, West Haven
- 3Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut
- 4Biomedical Informatics & Data Science, Yale School of Medicine, New Haven, Connecticut
- 5Research and Development, VA Puget Sound Health Care System, Seattle, Washington
- 6Health Management and Policy, College of Health, Center for Quantitative Life Sciences, Oregon State University, Corvallis
- 7Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut
- 8Divisions of Gastroenterology, VA Puget Sound Health Care System and University of Washington, Seattle
- 9Division of Infectious Diseases, Department of Medicine, Oregon Health and Science University, Portland
Abstract
Importance: In clinical trials, the messenger RNA (mRNA)–1345 vaccine provided protection against respiratory syncytial virus (RSV) illness. Data on mRNA-1345 effectiveness in broader patient populations are needed.
Objective: To estimate the effectiveness of mRNA-1345 vaccination during a single respiratory illness season.
Design, Setting, and Participants: This cohort study used a target trial emulation framework to assess veterans 50 years and older receiving care in the Veterans Health Administration. Eligible vaccine recipients were matched with up to 4 unvaccinated individuals in 4 monthly, nested, sequential trials from October 1, 2025, to January 31, 2026. Outcomes were ascertained through May 31, 2026, or 24 weeks.
Exposure: A single dose of mRNA-1345 RSV vaccine vs no RSV vaccination.
Main Outcomes and Measures: The primary outcome was any positive RSV test result from day 14 after the matched index date. Secondary outcomes included RSV-associated emergency department (ED) or urgent care (UC) encounters and RSV-associated hospitalizations. Vaccine effectiveness was estimated as 100 × (1 – risk ratio). A sensitivity analysis comparing veterans who received same-day mRNA-1345 and influenza vaccination to influenza vaccination alone (active comparator arm) was performed to explore potential bias from differences in health care–seeking behavior and outcome ascertainment between comparator groups.
Results: A total of 74 926 vaccinated veterans were matched to 286 425 unique control individuals, weighted to represent 74 926 individuals, for a total of 149 852 study participants (median [IQR] age, 73.0 [63.3-78.6] years; 136 756 [91.3%] male). During a median (IQR) follow-up of 160 (130-168) days, estimated vaccine effectiveness was 60.3% (95% CI, 49.0%-70.4%) against any documented infection, 60.2% (95% CI, 47.2%-71.5%) against RSV-associated ED or UC encounters, and 81.8% (95% CI, 58.1%-99.9%) against RSV-associated hospitalizations. Estimated effectiveness against documented infections decreased with increasing age, from 82.9% (95% CI, 64.0%-96.7%) in the 50- to 59-year age group to 28.6% (95% CI, −12.0% to 60.4%) in the 80-year or older age group. With an active comparator arm, estimated effectiveness was 67.1% (95% CI, 48.9%-82.6%) against documented RSV infections, 69.5% (95% CI, 49.7%-85.4%) against RSV-associated ED and UC encounters, and 86.9% (95% CI, 56.5%-100.0%) against RSV-associated hospitalizations.
Conclusions and Relevance: In this cohort study using a target trial emulation of mRNA-1345 vaccine effectiveness during 24 weeks, vaccination was associated with protection against RSV illness and associated health care use in adults 50 years and older. Comparative effectiveness studies are needed to determine the relative benefits of available RSV vaccine products.
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BibTeX
@article{bui2026effectiveness,
title = {{Effectiveness of the mRNA-1345 Vaccine Against Respiratory Syncytial Virus in US Veterans}},
author = {David P. Bui and Lei Yan and Yuli Li and Nallakkandi Rajeevan and Robert Vergun and Vyshnika Sriskantharajah and Denise M. Hynes and Kristin Berry and Yuan Huang and Hung-Mo Lin and Mihaela Aslan and George N. Ioannou and Kristina L. Bajema},
journal = {JAMA Network Open},
year = {2026},
month = oct,
doi = {10.1001/jamanetworkopen.2026.40981},
url = {https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2855917},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Effectiveness of the mRNA-1345 Vaccine Against Respiratory Syncytial Virus in US Veterans
AU - David P. Bui
AU - Lei Yan
AU - Yuli Li
AU - Nallakkandi Rajeevan
AU - Robert Vergun
AU - Vyshnika Sriskantharajah
AU - Denise M. Hynes
AU - Kristin Berry
AU - Yuan Huang
AU - Hung-Mo Lin
AU - Mihaela Aslan
AU - George N. Ioannou
AU - Kristina L. Bajema
PY - 2026
DA - 2026/10/01
JO - JAMA Network Open
DO - 10.1001/jamanetworkopen.2026.40981
UR - https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2855917
AB - Importance: In clinical trials, the messenger RNA (mRNA)–1345 vaccine provided protection against respiratory syncytial virus (RSV) illness. Data on mRNA-1345 effectiveness in broader patient populations are needed. Objective: To estimate the effectiveness of mRNA-1345 vaccination during a single respiratory illness season. Design, Setting, and Participants: This cohort study used a target trial emulation framework to assess veterans 50 years and older receiving care in the Veterans Health Administration. Eligible vaccine recipients were matched with up to 4 unvaccinated individuals in 4 monthly, nested, sequential trials from October 1, 2025, to January 31, 2026. Outcomes were ascertained through May 31, 2026, or 24 weeks. Exposure: A single dose of mRNA-1345 RSV vaccine vs no RSV vaccination. Main Outcomes and Measures: The primary outcome was any positive RSV test result from day 14 after the matched index date. Secondary outcomes included RSV-associated emergency department (ED) or urgent care (UC) encounters and RSV-associated hospitalizations. Vaccine effectiveness was estimated as 100 × (1 – risk ratio). A sensitivity analysis comparing veterans who received same-day mRNA-1345 and influenza vaccination to influenza vaccination alone (active comparator arm) was performed to explore potential bias from differences in health care–seeking behavior and outcome ascertainment between comparator groups. Results: A total of 74 926 vaccinated veterans were matched to 286 425 unique control individuals, weighted to represent 74 926 individuals, for a total of 149 852 study participants (median [IQR] age, 73.0 [63.3-78.6] years; 136 756 [91.3%] male). During a median (IQR) follow-up of 160 (130-168) days, estimated vaccine effectiveness was 60.3% (95% CI, 49.0%-70.4%) against any documented infection, 60.2% (95% CI, 47.2%-71.5%) against RSV-associated ED or UC encounters, and 81.8% (95% CI, 58.1%-99.9%) against RSV-associated hospitalizations. Estimated effectiveness against documented infections decreased with increasing age, from 82.9% (95% CI, 64.0%-96.7%) in the 50- to 59-year age group to 28.6% (95% CI, −12.0% to 60.4%) in the 80-year or older age group. With an active comparator arm, estimated effectiveness was 67.1% (95% CI, 48.9%-82.6%) against documented RSV infections, 69.5% (95% CI, 49.7%-85.4%) against RSV-associated ED and UC encounters, and 86.9% (95% CI, 56.5%-100.0%) against RSV-associated hospitalizations. Conclusions and Relevance: In this cohort study using a target trial emulation of mRNA-1345 vaccine effectiveness during 24 weeks, vaccination was associated with protection against RSV illness and associated health care use in adults 50 years and older. Comparative effectiveness studies are needed to determine the relative benefits of available RSV vaccine products.
SN - 2574-3805
ER -