Phase 1 Safety and Immunogenicity Study of a Respiratory Syncytial Virus Vaccine With an Adenovirus 26 Vector Encoding Prefusion F (Ad26.RSV.preF) in Adults Aged ≥60 Years

J Infect Dis. 2020 Aug 17;222(6):979-988. doi: 10.1093/infdis/jiaa193.

Abstract

Background: Despite the high disease burden of respiratory syncytial virus (RSV) in older adults, there is no approved vaccine. We evaluated the experimental RSV vaccine, Ad26.RSV.preF, a replication-incompetent adenovirus 26 vector encoding the F protein stabilized in prefusion conformation.

Methods: This phase 1 clinical trial was performed in healthy adults aged ≥60 years. Seventy-two participants received 1 or 2 intramuscular injections of low-dose (LD; 5 × 1010 vector particles) or high-dose (HD; 1 × 1011 vector particles) Ad26.RSV.preF vaccine or placebo, with approximately 12 months between doses and 2-year follow-up for safety and immunogenicity outcomes.

Results: Solicited adverse events were reported by 44% of vaccine recipients and were transient and mild or moderate in intensity. No serious adverse events were related to vaccination. After the first vaccination, geometric mean titers for RSV-A2 neutralization increased from baseline (432 for LD and 512 for HD vaccine) to day 29 (1031 for LD and 1617 for HD). Pre-F-specific antibody geometric mean titers and median frequencies of F-specific interferon γ-secreting T cells also increased substantially from baseline. These immune responses were still maintained above baseline levels 2 years after immunization and could be boosted with a second immunization at 1 year.

Conclusions: Ad26.RSV.preF (LD and HD) had an acceptable safety profile and elicited sustained humoral and cellular immune responses after a single immunization in older adults.

Keywords: respiratory syncytial virus; adenovirus vectors; durable immune responses; immunogenicity; prefusion F; vaccine; vaccine safety.

Publication types

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

MeSH terms

  • Adenoviridae* / genetics
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Female
  • Genetic Vectors* / genetics
  • Humans
  • Immunity, Cellular
  • Immunogenicity, Vaccine
  • Male
  • Middle Aged
  • Respiratory Syncytial Virus Infections / prevention & control*
  • Respiratory Syncytial Virus Vaccines / adverse effects
  • Respiratory Syncytial Virus Vaccines / genetics
  • Respiratory Syncytial Virus Vaccines / immunology*
  • Respiratory Syncytial Virus, Human / genetics
  • Respiratory Syncytial Virus, Human / immunology*
  • Vaccination
  • Viral Fusion Proteins / genetics
  • Viral Fusion Proteins / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • F protein, human respiratory syncytial virus
  • Respiratory Syncytial Virus Vaccines
  • Viral Fusion Proteins