Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F (RSVPreF3) Candidate Vaccine in Older Adults: Phase 1/2 Randomized Clinical Trial

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The aim of this study was to investigate safety and immunogenicity of vaccine formulations against respiratory syncytial virus (RSV) containing the stabilized prefusion conformation of RSV fusion protein (RSVPreF3).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This phase 1/2, randomized controlled, observer-blind study enrolled 48 young adults (YAs; aged 18–40 years) and 1005 older adults (OAs; aged 60–80 years) between January and August 2019. Participants were randomized into equally sized groups to receive 2 doses of unadjuvanted (YAs and OAs) or AS01-adjuvanted (OAs) vaccine or placebo 2 months apart. Vaccine safety and immunogenicity were assessed until 1 month (YAs) or 12 months (OAs) after second vaccination.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The RSVPreF3 vaccines boosted humoral (RSVPreF3-specific immunoglobulin G [IgG] and RSV-A neutralizing antibody) responses, which increased in an antigen concentration-dependent manner and were highest after dose 1. Compared to prevaccination, the geometric mean frequencies of polyfunctional CD4+ T cells increased after each dose and were significantly higher in adjuvanted than unadjuvanted vaccinees. Postvaccination immune responses persisted until end of follow-up. Solicited adverse events were mostly mild to moderate and transient. Despite a higher observed reactogenicity of AS01-containing vaccines, no safety concerns were identified for any assessed formulation.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Based on safety and immunogenicity profiles, the AS01E-adjuvanted vaccine containing 120 μg of RSVPreF3 was selected for further clinical development.</jats:p></jats:sec><jats:sec><jats:title>Clinical Trials Registration</jats:title><jats:p>NCT03814590.</jats:p></jats:sec>