In an international, phase 3 trial of 24,966 older adults, a single dose of an AS01E-adjuvanted respiratory syncytial virus (RSV) prefusion F protein–based candidate vaccine (RSVPreF3 OA) was safe and prevented RSV-related acute respiratory infection and lower respiratory tract disease and severe RSV-related lower respiratory tract disease, researchers report.
Adults 60 years of age or older were randomized to a single dose of an RSVPreF3 OA or placebo before the RSV season. Based on a primary objective of showing vaccine efficacy and safety during the RSV season, the study showed the following: “Over a median follow-up of 6.7 months, vaccine efficacy against RT-PCR–confirmed RSV-related lower respiratory tract disease was 82.6% (96.95% confidence interval [CI], 57.9 to 94.1), with 7 cases (1.0 per 1000 participant-years) in the vaccine group and 40 cases (5.8 per 1000 participant-years) in the placebo group. Vaccine efficacy was 94.1% (95% CI, 62.4 to 99.9) against severe RSV-related lower respiratory tract disease (assessed on the basis of clinical signs or by the investigator) and 71.7% (95% CI, 56.2 to 82.3) against RSV-related acute respiratory infection. Vaccine efficacy was similar against the RSV A and B subtypes (for RSV-related lower respiratory tract disease: 84.6% and 80.9%, respectively; for RSV-related acute respiratory infection: 71.9% and 70.6%, respectively). High vaccine efficacy was observed in various age groups and in participants with coexisting conditions. The RSVPreF3 OA vaccine was more reactogenic than placebo, but most adverse events for which reports were solicited were transient, with mild-to-moderate severity. The incidences of serious adverse events and potential immune-mediated diseases were similar in the two groups.”
Editorial: Reflecting on this and another RSV vaccine study in this issue of NEJM, an editorialist writes: “Notably, the success of structure-based vaccine design for RSV informed the rapid response to Covid-19. Outbreaks of Middle East respiratory syndrome coronavirus were occurring while the RSV preF structure was being analyzed. At that time, we did not know the atomic-level structure of any coronavirus protein, but over the next few years, spike protein structures were solved, and ultimately stabilizing mutations were identified to maintain the prefusion spike conformation and improve protein expression levels. These studies were the basis for coronavirus pandemic preparedness planning that included public–private and academic collaborations that were operative in 2019. Because of the technical advances in biomedical science and the RSV blueprint, work that had taken decades in RSV research was compressed into just a few weeks for SARS-CoV-2, providing sequences, structures, and reagents needed to rapidly develop safe and effective vaccines and therapeutic [monoclonal antibodies].
“With Covid-19 vaccines now approved for clinical use and RSV vaccines shown to be effective and awaiting approval, we have entered an era of precision antigen design based on protein engineering guided by atomic-level structure. I hope these advances will lead to future successes in addressing unmet needs and combating threats from emerging pathogens.”