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

J Infect Dis. 2023 Mar 28;227(6):761-772. doi: 10.1093/infdis/jiac327.

Abstract

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 AS01E-adjuvanted vaccine containing 120 μg of RSVPreF3 was selected for further clinical development.

Clinical trials registration: NCT03814590.

Keywords: AS01 adjuvant; F protein; RSV neutralizing antibodies; cell-mediated immunity; respiratory syncytial virus.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Humans
  • Immunogenicity, Vaccine
  • Respiratory Syncytial Virus Infections* / prevention & control
  • Respiratory Syncytial Virus Vaccines*
  • Respiratory Syncytial Virus, Human*
  • Young Adult

Substances

  • Respiratory Syncytial Virus Vaccines
  • Antibodies, Viral
  • Antibodies, Neutralizing

Associated data

  • ClinicalTrials.gov/NCT03814590