Safety and Immunogenicity of 3 Formulations of an Investigational Respiratory Syncytial Virus Vaccine in Nonpregnant Women: Results From 2 Phase 2 Trials

J Infect Dis. 2018 Apr 23;217(10):1616-1625. doi: 10.1093/infdis/jiy065.

Abstract

Background: Respiratory syncytial virus (RSV) causes bronchiolitis and pneumonia in neonates and infants. RSV vaccination during pregnancy could boost preexisting neutralizing antibody titers, providing passive protection to newborns.

Methods: Two observer-blinded, controlled studies (RSV F-020 [clinical trials registration NCT02360475] and RSV F-024 [NCT02753413]) evaluated immunogenicity and safety of an investigational RSV vaccine in healthy, nonpregnant 18-45-year-old women. Both studies used a licensed adult formulation of combined tetanus toxoid-diphtheria toxoid-acellular pertussis (Tdap) vaccine as a control. RSV F-020 evaluated immunogenicity and safety: participants were randomized (1:1:1:1) to receive 1 dose of RSV-prefusion F protein (PreF) vaccine containing 30 µg or 60 µg of nonadjuvanted RSV-PreF, 60 µg of aluminum-adjuvanted RSV-PreF, or Tdap. RSV F-024 evaluated safety: participants were randomized 1:1 to receive 1 dose of 60 µg of nonadjuvanted RSV-PreF or Tdap.

Results: Both studies showed similar reactogenicity profiles for RSV-PreF and Tdap. No serious adverse events were considered vaccine related. In RSV F-020, geometric mean ratios of RSV-A neutralizing antibody levels at day 30 versus prevaccination were 3.1-3.9 in RSV-PreF recipients and 0.9 in controls. Palivizumab-competing antibody concentrations increased >14-fold in RSV-PreF recipients on day 30. RSV antibody titers waned after day 30 but remained well above baseline through day 90.

Conclusions: All formulations of RSV-PreF boosted preexisting immune responses in 18-45-year old women with comparable immunogenicity. The RSV-PreF safety profile was similar to that of Tdap vaccine.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Adolescent
  • Adult
  • Antibodies, Bacterial / immunology
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Diphtheria-Tetanus-Pertussis Vaccine / immunology
  • Diphtheria-Tetanus-acellular Pertussis Vaccines / immunology
  • Female
  • Humans
  • Immunogenicity, Vaccine / immunology*
  • Middle Aged
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Vaccines / adverse effects*
  • Respiratory Syncytial Virus Vaccines / immunology*
  • Respiratory Syncytial Virus, Human / immunology*
  • Vaccination / methods
  • Whooping Cough / immunology
  • Young Adult

Substances

  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Diphtheria-Tetanus-Pertussis Vaccine
  • Diphtheria-Tetanus-acellular Pertussis Vaccines
  • Respiratory Syncytial Virus Vaccines

Associated data

  • ClinicalTrials.gov/NCT02360475
  • ClinicalTrials.gov/NCT02753413