In adults aged 60 years or older, a single dose of an mRNA-based respiratory syncytial virus (RSV) vaccine encoding the stabilized RSV prefusion F glycoprotein reduced the incidence of RSV-associated lower respiratory tract disease and of RSV-associated acute respiratory disease without safety concerns, researchers report. The international, phase 2/3 ConquerRSV trial of mRNA-1345 “showed 83.7% efficacy against RSV-associated lower respiratory tract disease with at least two signs or symptoms, 82.4% efficacy against RSV-associated lower respiratory tract disease with at least three signs or symptoms, and 68.4% against RSV-associated acute respiratory disease,” the authors write.
Participants were randomized to receive a 50-μg dose of mRNA-1345 or placebo. Based on primary efficacy endpoints of the prevention of RSV-associated lower respiratory tract disease with at least 2 signs or symptoms and with at least 3 signs or symptoms, the study showed: “Overall, 35,541 participants were assigned to receive the mRNA-1345 vaccine (17,793 participants) or placebo (17,748). The median follow-up was 112 days (range, 1 to 379). The primary analyses were conducted when at least 50% of the anticipated cases of RSV-associated lower respiratory tract disease had occurred. Vaccine efficacy was 83.7% (95.88% confidence interval [CI], 66.0 to 92.2) against RSV-associated lower respiratory tract disease with at least two signs or symptoms and 82.4% (96.36% CI, 34.8 to 95.3) against the disease with at least three signs or symptoms. Vaccine efficacy was 68.4% (95% CI, 50.9 to 79.7) against RSV-associated acute respiratory disease. Protection was observed against both RSV subtypes (A and B) and was generally consistent across subgroups defined according to age and coexisting conditions. Participants in the mRNA-1345 group had a higher incidence than those in the placebo group of solicited local adverse reactions (58.7% vs. 16.2%) and of systemic adverse reactions (47.7% vs. 32.9%); most reactions were mild to moderate in severity and were transient. Serious adverse events occurred in 2.8% of the participants in each trial group.”
Editorial: “As often happens with lifesaving immunizations, RSV vaccines are being initially produced and approved for use in high-income countries, although efforts are under way by the Bill and Melinda Gates Foundation and others to help ensure access to RSV vaccines for pregnant persons in lower-income countries,” editorialists write. “There are also phase 1 clinical trials planned or under way to evaluate mRNA RSV vaccines in pregnant persons and in children, which may provide more tools for preventing RSV infection in the future. As [this article] exemplifies, the development of safe and effective vaccines against RSV has been a long and tortuous journey marked by setback and discovery but that now stands poised to have substantial effects on public health.”