Respiratory syncytial virus vaccine effectiveness among US veterans, September, 2023 to March, 2024: a target trial emulation study

Abstract

Background: New respiratory syncytial virus (RSV) vaccines have been approved in the USA for the prevention of RSV-associated lower respiratory tract disease in adults aged 60 years and older. Information on the real-world effectiveness of these vaccines is needed.

Methods: We used electronic health records in the Veterans Health Administration to emulate a target trial comparing a single dose of a recombinant stabilised prefusion F protein RSV vaccine versus no vaccination among veterans aged 60 years and older. We matched eligible vaccine recipients with up to four unvaccinated individuals in four monthly nested sequential trials from Sept 1 to Dec 31, 2023. Outcomes were ascertained up to March 31, 2024. The primary outcome was any positive RSV test from day 14 following the matched index date. Secondary outcomes included hospitalisation and emergency department or urgent care encounter occurring within 1 day before or after a positive RSV test. We estimated vaccine effectiveness as 100 × (1 - risk ratio).

Findings: We included 146 852 vaccinated individuals matched to 582 936 unique control individuals, weighted equally to represent 146 852 individuals. Across the two groups, 276 039 (94·0%) of 293 704 veterans were male, 17 665 (6·0%) were female, and median age was 75·9 years (IQR 71·7-79·7). Over a median follow-up of 124 days (IQR 102-150), the incidence rate of documented RSV infection was 1·7 (95% CI 1·4-2·1) events per 1000 person-years (88 total events) in the vaccinated group and 7·3 (6·6-8·1) per 1000 person-years in the unvaccinated group (372 total events), and vaccine effectiveness was estimated as 78·1% (72·6-83·5). Among the secondary outcomes, vaccine effectiveness was estimated at 78·7% (72·2-84·8) against RSV-associated emergency department or urgent care encounters, and 80·3% (65·8-90·1) against RSV-associated hospitalisation.

Interpretation: RSV vaccination was effective in preventing RSV-related illness, including associated health-care use, in adults aged 60 years and older during the 2023-24 respiratory illness season, supporting current recommendations for vaccination in this population.

Funding: US Department of Veterans Affairs Cooperative Studies Program, US Department of Health and Human Services Biomedical Advanced Research and Development Authority, and US Food and Drug Administration.