mRNA RSV Vaccine Candidate Found Effective But With Adverse Events

Before 2023, there were no immunizing tools to protect older adults from illness and death due to respiratory syncytial virus (RSV). This year, the U.S. Food and Drug Administration approved two RSV vaccines for older adults.

According to an Original Article published today by the New England Journal of Medicine, an mRNA-based vaccine was found to be very effective at protecting healthy adults. 

In this ModernaTX, Inc. sponsored ongoing, randomized, double-blind, placebo-controlled, phase 2/3 clinical trial, participants were randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive one dose of mRNA-1345 (50 μg) or placebo.

The two primary efficacy endpoints were preventing RSV-associated lower respiratory tract disease with at least two signs or symptoms and at least three signs or symptoms. A key secondary efficacy endpoint was the prevention of RSV-associated acute respiratory disease. Safety was also assessed.

Overall, 17,793 participants were assigned to receive the mRNA-1345 vaccine candidate. 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 systemic adverse reactions (47.7% vs. 32.9%). Most of these reactions were mild to moderate in severity and were transient.

However. serious adverse events occurred in 2.8% of the participants in each trial group.

In summary, these researchers wrote, 'This phase 2–3 efficacy trial showed that a single 50-μg dose of the mRNA-1345 vaccine in adults 60 or older was efficacious against a spectrum of RSV-confirmed respiratory disease.'