Immune persistence and safety of the AS01E-adjuvanted respiratory syncytial virus prefusion F protein-based vaccine in adults 50-59 years of age, including at-increased-risk adults: A randomized controlled trial.

In this phase 3, randomized, placebo-controlled multi-country study, the AS01E-adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine (adjuvanted RSVPreF3) was immunologically non-inferior at 1 month post-vaccination in adults 50-59 years of age (YOA) compared to adults ≥60 YOA, in whom efficacy was previously demonstrated. Here, we report end-of-study immunogenicity and safety results until 12 months post-vaccination. Participants 50-59 YOA were divided into an at-increased-risk (AIR) and a non-AIR subcohort, each randomized (2:1) to receive one dose of adjuvanted RSVPreF3 or placebo. A control cohort of participants ≥60 YOA received adjuvanted RSVPreF3. Humoral/cell-mediated immunity and safety were assessed. In total, 1152 participants 50-59 YOA received adjuvanted RSVPreF3 or placebo, and 381 participants ≥60 YOA received adjuvanted RSVPreF3. In all vaccinated groups, RSV-A and RSV-B neutralizing titers and RSVPreF3-specific polyfunctional CD4+ T-cell frequencies increased at 1 month post-vaccination and declined thereafter, but remained above baseline and placebo levels at 6 and 12 months post-vaccination. During the study, one vaccine-related serious adverse event (cold-type hemolytic anemia in a participant ≥60 YOA) was reported. Five participants died (all in the 50-59 YOA AIR subcohort, four had received adjuvanted RSVPreF3, one placebo); none of the deaths were considered vaccine-related. In conclusion, adjuvanted RSVPreF3 induced a humoral and cell-mediated immune response persisting until at least 12 months post-vaccination in adults 50-59 YOA, including those at increased risk for RSV disease. The vaccine had an acceptable 12-month safety profile in adults 50-59 YOA, consistent with that in adults ≥60 YOA.Trial Registration: ClinicalTrials.gov: NCT05590403.