Efficacy, Safety, and Immunogenicity of the MATISSE (Maternal Immunization Study for Safety and Efficacy) Maternal Respiratory Syncytial Virus Prefusion F Protein Vaccine Trial.

Summary

In this global phase 3 RCT of 7,420 pregnant participants, maternal RSVpreF vaccination reduced severe, medically attended infant RSV lower respiratory tract illness by 82.4% at 90 days and 70.0% at 180 days post birth. The vaccine elicited robust maternal responses and efficient antibody transfer to newborns with no new safety signals.

Key Findings

• Vaccine efficacy against severe, medically attended infant RSV LRTI was 82.4% (90 days) and 70.0% (180 days).
• Robust maternal immune responses with highly efficient transplacental transfer across multiple subgroups.
• Final safety profile remained consistent with primary analysis with no new safety concerns.

Clinical Implications

Supports widespread implementation of maternal RSVpreF vaccination to prevent severe infant RSV illness up to 6 months, with strong maternal–neonatal immunogenicity and reassuring safety.

Limitations

• Efficacy reported through 180 days; longer-term infant outcomes were not assessed.
• Immunogenicity assessed in a subset; regional heterogeneity in outcomes requires continued monitoring (addressed in companion analyses).

Future Directions

Assess durability beyond 6 months, co-administration strategies, real-world effectiveness across regions, and integration with infant monoclonal prevention programs.