Randomized, placebo-controlled phase 3 trial evaluating safety, immunogenicity, and reactogenicity of RSVPreF3-Mat in high-risk pregnant women and their infants.
In high-risk pregnant women, the RSVPreF3-Mat vaccine showed an acceptable safety profile and induced strong immune responses, but preterm birth rates were similar to placebo.
Where it sits
this study against the rest of the lanreotide corpusSummary and findings
This phase 3 trial evaluated the safety, immunogenicity, and reactogenicity of the RSVPreF3-Mat vaccine in high-risk pregnant women. A total of 169 maternal participants received either the vaccine or placebo between 24 and 36 weeks of gestation. The study was unblinded due to an observed increased risk of preterm birth in another trial.
Abstract
Respiratory syncytial virus (RSV) causes respiratory illness among infants; maternal vaccination confers passive protection through placental antibody transfer. This phase 3, randomized, placebo-controlled trial evaluated safety, reactogenicity, and immunogenicity of RSV prefusion protein F3 maternal vaccine (RSVPreF3-Mat), administered at 24<sup>0/7</sup> to 36<sup>0/7</sup> weeks of gestation to high-risk pregnant women (women with obstetric complications and/or human immunodeficiency virus infection or in pregnant adolescents), and their infants up to 1 year post-birth. Enrollment was stopped and the study unblinded after an increased risk of preterm birth, associated with RSVPreF3 vaccine, was observed in another trial in healthy pregnant women. One hundred and sixty-nine maternal participants received either vaccine or placebo. No serious adverse events in maternal or infant participants were considered vaccine-related. Preterm birth occurred in 18.2% and 19.7% of participants in the vaccine and placebo groups, respectively, with one neonatal death in each group. In the vaccine group, increase in maternal neutralizing antibody titers against RSV subtype A and B was observed at Day 31 post-vaccination and remained high at delivery. Geometric mean ratio of titers at delivery over pre-vaccination for RSV A and B were 8.87- and 8.21-fold, respectively. Similarly, anti-RSVPreF3-Mat immunoglobulin G (IgG) levels showed increase at Day 31 post-vaccination and remained high at delivery (14.12-fold increase over pre-vaccination) with placental transfer ratio of RSVPreF3 IgG-specific antibodies at delivery of 1.33. In this study of high-risk pregnant women, RSVPreF3-Mat demonstrated an acceptable safety profile, induced robust immune responses with successful placental antibody transfer, and showed balanced rates of preterm birth between the groups. <b>Trial registration:</b> EudraCT: 2021-000994-96; NCT: NCT04980391.
Background
This study addresses the need for effective maternal vaccination against respiratory syncytial virus (RSV), which poses significant risks to infants. Prior knowledge indicated that maternal vaccination could confer passive immunity to infants through placental transfer of antibodies. The importance of this study lies in its evaluation of a specific vaccine's safety and immunogenicity in a high-risk population.
Methods
This was a phase 3, randomized, placebo-controlled trial involving 169 high-risk pregnant women. The vaccine was administered between 24 and 36 weeks of gestation. Primary outcomes included safety, reactogenicity, and immunogenicity, with secondary outcomes related to preterm birth rates.
Results
Preterm birth occurred in 18.2% of the vaccine group and 19.7% of the placebo group, indicating no significant difference between groups. Maternal neutralizing antibody titers against RSV increased significantly, with geometric mean ratios of 8.87 for RSV A and 8.21 for RSV B at delivery. Anti-RSVPreF3-Mat IgG levels increased by 14.12-fold over pre-vaccination, with a placental transfer ratio of 1.33.
Interpretation
The results show that the RSVPreF3-Mat vaccine induced robust immune responses without significant safety concerns in this high-risk population. However, the small differences in preterm birth rates suggest a need for caution in interpreting clinical significance. The study's limitations, including the unblinding due to safety concerns from another trial, may affect the reliability of the findings.
Key findings
- Preterm birth occurred in 18.2% of the vaccine group and 19.7% of the placebo group.
- Geometric mean ratio of neutralizing antibody titers at delivery over pre-vaccination for RSV A was 8.87-fold.
- Geometric mean ratio of neutralizing antibody titers at delivery over pre-vaccination for RSV B was 8.21-fold.
- Anti-RSVPreF3-Mat IgG levels showed a 14.12-fold increase over pre-vaccination.
- Placental transfer ratio of RSVPreF3 IgG-specific antibodies at delivery was 1.33.
Limitations
- Enrollment was stopped due to increased risk of preterm birth in another trial.
- Sample size was relatively small at n=169.
- Unblinded study design may introduce bias.