The trial did not meet the second primary efficacy endpoint of medically attended respiratory syncytial virus-associated lower respiratory tract illness.
New data from a phase 3 trial show that an investigative respiratory syncytial virus (RSV) vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants.
RSV is the most common cause of acute lower respiratory tract illness and a leading cause of death in infants younger than 6 months of age. Severe RSV-associated lower respiratory tract illness peaks in the first 2 to 3 months of age, despite naturally acquired maternal antibodies, and experts have been uncertain whether vaccination during pregnancy could reduce the burden of RSV in newborns and infants.
The prefusion form of the RSV fusion F glycoprotein (preF) is a major target for potential RSV vaccines. The investigational bivalent RSVpreF vaccine contains stabilized preF glycoproteins from the 2 main circulating subgroups and has shown promise in pregnant women in a phase 2b, proof-of-concept trial.
The phase 3 Maternal Immunization Study for Safety and Efficacy (MATISSE) trial evaluated the efficacy and safety of maternal vaccination with RSVpreF in preventing RSV-associated lower respiratory tract illness in infants. The trial was a double-blind trial conducted in 18 countries, in which investigators randomly assigned pregnant women at 24 to 36 weeks’ gestation to receive a single intramuscular 120-μg dose of the RSVpreF vaccine or placebo.
The 2 primary efficacy endpoints were medically attended severe RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth. A lower boundary of the confidence interval for vaccine efficacy greater than 20% was considered to meet the success criterion for vaccine efficacy regarding the primary endpoints.
At the prespecified interim analysis, the success criterion for vaccine efficacy was met with medically attended severe lower respiratory tract illness occurring within 90 days after birth but was not met with regard to medically attended RSV-associated lower respiratory tract illness.
Overall, 3682 maternal participants received the vaccine and 3676 received the placebo, and 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group, demonstrating a vaccine efficacy of 81.8%. Additionally, 19 and 62 cases, respectively, occurred within 180 days after birth, demonstrating an efficacy of 69.4%.
Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group, demonstrating a vaccine efficacy of 57.1%. These results did not meet the statistical success criterion.
No safety signals were detected in maternal participants or in infants and toddlers up to 2 years of age. The incidences of adverse events (AEs) reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% of women and 34.5% of infants).
The safety and AE profile in maternal participants was consistent with those previously reported in phase 1 and 2 clinical studies of adults, with mostly mild to moderate reactogenicity and AE and serious AE profiles similar to those of the placebo. The investigators said it is reassuring that no safety concerns were detected in the infants or mothers in the trial, although they noted that the number of participants was small and an analysis of the final trial data, including safety data, is underway.
Kampmann B, Madhi SA, Munjal I, Simoes EAF, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. New Engl J Med. doi:10.1056/NEJMoa2216480.