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

Background 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). Methods 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. Results 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. Conclusions Based on safety and immunogenicity profiles, the AS01(E)-adjuvanted vaccine containing 120 mu g of RSVPreF3 was selected for further clinical development. Vaccine formulations against respiratory syncytial virus (RSV) containing the stabilized prefusion conformation of RSV fusion protein (RSVPreF3) were well tolerated and immunogenic. Based on safety/immunogenicity profiles, the AS01(E)-adjuvanted vaccine containing 120 mu g of RSVPreF3 was selected for further clinical development.

Automated summary

The safety and immunogenicity of vaccine formulations containing the stabilized prefusion conformation of RSV fusion protein (RSVPreF3) against respiratory syncytial virus (RSV) were investigated. The results showed that these vaccines effectively boosted humoral immune responses and increased the frequencies of polyfunctional CD4(+) T cells. Most adverse events were mild to moderate, and the safety of the vaccines was confirmed. Based on safety and immunogenicity profiles, the AS01(E)-adjuvanted vaccine containing 120 μg of RSVPreF3 was selected for further clinical development.