Safety and Immunogenicity of Respiratory Syncytial Virus Pre-fusion Maternal Vaccine Co-administered with Diphtheria-Tetanus-Pertussis Vaccine: A Phase 2 Study

J Infect Dis. 2023 Dec 22:jiad560. doi: 10.1093/infdis/jiad560. Online ahead of print.

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, non-pregnant women, randomized 1:1:1:1:1 to five parallel groups studying RSVPreF3 (60 or 120 µg) co-administered with diphtheria, tetanus, and acellular pertussis vaccine (dTpa) or placebo, and dTpa co-administered with placebo. Safety and humoral immune responses were assessed. An extension phase also assessed a RSVPreF3 120 μg vaccination 12-18 months post-first vaccination.

Results: The safety profile of RSVPreF3 was unaffected by dose or dTpa co-administration. Solicited and unsolicited adverse events (AEs) were evenly distributed across study groups. Injection-site pain was higher following the second vaccination vs 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 post-vaccination, which persisted at 12-18 months post-vaccination; modest 2-fold increases were observed with a second RSVPreF3 vaccination.

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

Clinical trials registration: NCT04138056.

Keywords: RSV vaccine; Respiratory syncytial virus; co-administration; dTpa vaccine; immunogenicity; maternal vaccine; safety.

Associated data

  • ClinicalTrials.gov/NCT04138056