Efficacy, Immunogenicity, and Safety of an Investigational Maternal Respiratory Syncytial Virus Prefusion F Protein-Based Vaccine

Clin Infect Dis. 2026 Feb 9;82(1):e146-e155. doi: 10.1093/cid/ciaf033.

Abstract

Background: In this phase 3 trial of an investigational maternal respiratory syncytial virus prefusion F protein-based vaccine (RSVPreF3-Mat), a higher rate of preterm birth was observed in the vaccine (6.8%) versus the placebo group (4.9%). Trial enrollment and vaccination were stopped. Results of investigations into this safety signal were reported previously. Here, we describe end-of-trial efficacy, immunogenicity, and safety results.

Methods: Women 18-49 years old were randomized 2:1 to receive 1 dose of RSVPreF3-Mat (n = 3557) or placebo (n = 1771) at 240/7-340/7 weeks' gestation. Primary outcomes were any and severe medically assessed RSV-associated lower respiratory tract disease (MA-RSV-LRTD) in infants until 6 months postbirth and safety until 12 months postbirth. Other efficacy outcomes were evaluated, along with immunogenicity (until 6 months postpartum/birth) and safety in mothers and infants.

Results: Efficacy (with 95% credible interval) in infants until 6 months postbirth was 65.5% (37.5%-82.0%) against any MA-RSV-LRTD, 69.0% (33.0%-87.6%) against severe MA-RSV-LRTD, and 50.1% (-3.6% to 75.8%) against RSV hospitalization; it waned over time thereafter. Efficacy against MA-RSV-LRTD was 47.8% (-25.8% to 77.3%) in low- and middle-income and 75.9% (46.1%-91.5%) in high-income countries. RSVPreF3-Mat induced a substantial increase in RSV-A neutralization titers in mothers, with efficient transplacental transfer of antibodies that persisted in infants until at least 6 months postbirth.

Conclusions: Consistent with the high titers of transplacentally transferred antibodies, this trial suggests a reduced risk of any/severe MA-RSV-LRTD and RSV hospitalization until 6 months postbirth in infants born to mothers immunized with RSVPreF3-Mat during pregnancy. However, vaccine development was terminated due to an identified preterm birth risk. Clinical Trials Registration. NCT04605159.

Keywords: maternal immunization; prefusion F protein; preterm birth; respiratory syncytial virus; transplacental transfer.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase III

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Female
  • Humans
  • Immunogenicity, Vaccine*
  • Infant
  • Infant, Newborn
  • Middle Aged
  • Pregnancy
  • Pregnancy Complications, Infectious* / prevention & control
  • 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
  • Vaccine Efficacy
  • Viral Fusion Proteins* / immunology
  • Young Adult

Substances

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

Associated data

  • ClinicalTrials.gov/NCT04605159