Immunogenicity and Safety of the AS01E-adjuvanted Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine in Adults Aged 18-49 Years at Increased Risk of RSV Disease Compared with Adults Aged ≥60 Years.

Abstract

The AS01E-adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine (adjuvanted RSVPreF3) is approved for ≥60-year-olds and 50-59-year-olds at increased risk of RSV disease. We evaluated the vaccine's immunogenicity and safety in 18-49-year-olds at increased risk of RSV disease due to certain chronic conditions. This open-label, multicountry phase 3b trial included 18-49-year-olds at increased risk (at-risk 18-49 group) and a control group of ≥60-year-olds with or without chronic conditions (≥60 group). Primary objective was to demonstrate immunological noninferiority to adjuvanted RSVPreF3 in the at-risk 18-49 versus ≥60 group, based on group RSV-A/RSV-B geometric mean titer ratios and seroresponse rate differences 1 month postvaccination. Humoral, cell-mediated immunogenicity, and safety were assessed until 6 months postvaccination. Overall, 1458 adults were vaccinated. Immunological noninferiority was demonstrated in the at-risk 18-49 versus ≥60 group at 1 month postvaccination. Both groups showed increased RSV-A/RSV-B neutralizing titers and RSVPreF3-specific CD4+ T-cell frequencies at 1 month postvaccination that declined but remained above baseline at 6 months. Solicited events were more frequent in the at-risk 18-49 (84.3%) than in the ≥60 group (69.4%); most were mild-to-moderate and transient. Rates and intensity of unsolicited adverse events (AEs) were comparable across groups, with low reporting of serious AEs and AEs of special interest. Adjuvanted RSVPreF3 was immunologically noninferior in 18-49-year-olds with underlying conditions compared with ≥60-year-olds in whom efficacy was previously demonstrated, supporting efficacy inference in this younger population. Up to 6 months postvaccination, the vaccine elicited robust immune responses, and the safety profile was acceptable. Clinical Trial Registration: NCT06389487.