Safety and Immunogenicity of Respiratory Syncytial Virus Prefusion Maternal Vaccine Coadministered With Diphtheria-Tetanus-Pertussis Vaccine: A Phase 2 Study

J Infect Dis. 2024 Aug 16;230(2):e353-e362. doi: 10.1093/infdis/jiad560.

Abstract

Background: Respiratory syncytial virus (RSV) fusion protein stabilized in the prefusion conformation (RSVPreF3) was under investigation as a maternal vaccine.

Methods: This phase 2, randomized, placebo-controlled, single-dose, multicenter study enrolled healthy, nonpregnant women, randomized 1:1:1:1:1 to 5 parallel groups studying RSVPreF3 (60 or 120 µg) coadministered with diphtheria, tetanus, and acellular pertussis vaccine (dTpa) or placebo, and dTpa coadministered with placebo. Safety and humoral immune responses were assessed. An extension phase also assessed a RSVPreF3 120 μg vaccination 12-18 months after first vaccination.

Results: The safety profile of RSVPreF3 was unaffected by dose or dTpa coadministration. Solicited and unsolicited adverse events (AEs) were evenly distributed across study groups. Injection-site pain was higher following the second vaccination versus the first vaccination. Medically attended AEs were rare (<5% overall). Both RSVPreF3 dose levels (alone and with dTpa) were immunogenic, increasing levels of RSV-A neutralizing antibody ≥8-fold and anti-RSVPreF3 IgG antibody ≥11-fold at 1 month postvaccination, which persisted at 12-18 months postvaccination; modest 2-fold increases were observed with a second RSVPreF3 vaccination.

Conclusions: This study indicates RSVPreF3 coadministration with dTpa induces robust immune responses and is well tolerated, regardless of the RSVPreF3 dose level used.

Clinical trials registration: NCT04138056.

Keywords: RSV vaccine; coadministration; dTpa vaccine; immunogenicity; maternal vaccine; respiratory syncytial virus; safety.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral* / blood
  • Diphtheria-Tetanus-Pertussis Vaccine / administration & dosage
  • Diphtheria-Tetanus-Pertussis Vaccine / adverse effects
  • Diphtheria-Tetanus-Pertussis Vaccine / immunology
  • Diphtheria-Tetanus-acellular Pertussis Vaccines / administration & dosage
  • Diphtheria-Tetanus-acellular Pertussis Vaccines / adverse effects
  • Diphtheria-Tetanus-acellular Pertussis Vaccines / immunology
  • Female
  • Humans
  • Immunogenicity, Vaccine
  • Respiratory Syncytial Virus Infections* / immunology
  • Respiratory Syncytial Virus Infections* / prevention & control
  • Respiratory Syncytial Virus Vaccines* / administration & dosage
  • Respiratory Syncytial Virus Vaccines* / adverse effects
  • Respiratory Syncytial Virus Vaccines* / immunology
  • Respiratory Syncytial Virus, Human / immunology
  • Vaccination / adverse effects
  • Viral Fusion Proteins / administration & dosage
  • Viral Fusion Proteins / immunology
  • Young Adult

Substances

  • Antibodies, Viral
  • Respiratory Syncytial Virus Vaccines
  • Diphtheria-Tetanus-Pertussis Vaccine
  • Viral Fusion Proteins
  • Diphtheria-Tetanus-acellular Pertussis Vaccines

Associated data

  • ClinicalTrials.gov/NCT04138056

Grants and funding