Maternal RSV vaccination: clinical efficacy, safety, and global policy considerations: a systematic review

Respiratory syncytial virus (RSV) is among the leading causes of lower respiratory tract illness in newborns worldwide. This study reviews evidence on the efficacy and safety of maternal RSV vaccination.

PROSPERO registered this PRISMA-compliant systematic review (CRD42024566335). Keywords associated with RSV, respiratory infections, newborns, and immunisation were used in a search of PubMed/MEDLINE, Embase, Scopus, Web of Science, and Cochrane CENTRAL (inception to mid-2026). Because of the heterogeneity of the studies, a descriptive synthesis of the safety and efficacy data was performed instead of a formal meta-analysis.

Sixteen publications - four real-world studies and twelve generated from nine separate parent trials/datasets (including three subgroup or subset analyses and post-hoc studies from two RCTs) - met the inclusion criteria. Depending on the dose, formulation, and length of follow-up, maternal immunisation was linked to a lower incidence of severe RSV-related lower respiratory tract infections in newborns, with efficacy/effectiveness varying from roughly 39% to 100%. Trial-based efficacy results were generally in line with real-world effectiveness data from national and multicenter initiatives in the US, UK, and Argentina. Preterm birth outcomes differed depending on the formulation: a bivalent RSVpreF vaccine (Pfizer MATISSE trial; [Li, Y., Wang, X., Blau, D. M., Caballero, M. T., Feikin, D. R., Gill, C. J., Madhi, S. A., Omer, S. B., Simões, E. A. F., & Campbell, H. (2022). Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: A systematic analysis. The Lancet, 399(10340), 2047-2064; Otsuki, T., Akada, S., Anami, A., Kosaka, K., Munjal, I., Baber, J., Shoji, Y., Aizawa, M., Swanson, K. A., & Gurtman, A. (2024). Efficacy and safety of bivalent RSVpreF maternal vaccination to prevent RSV illness in Japanese infants: Subset analysis from the pivotal randomized phase 3 MATISSE trial. Vaccine, 42(22), 126041]) did not exhibit this association in post-hoc analyses, while an unadjuvanted RSVpreF vaccine (GSK; [Dieussaert, I., Hyung Kim, J., Luik, S., Seidl, C., Pu, W., Stegmann, J.-U., Swamy, G. K., Webster, P., & Dormitzer, P. R. (2024). RSV prefusion F protein-based maternal vaccine - preterm birth and other outcomes. New England Journal of Medicine, 390(11), 1009-1021]) showed a significant increase in preterm birth (RR 1.37, 95% CI 1.08-1.74). Although post-vaccination responses were frequent, they were usually mild to moderate.

There was no discernible rise in major adverse outcomes for mothers or newborns. Real-world data from a variety of situations now supports the conclusion that maternal RSV vaccination consistently decreased newborn RSV hospitalisation and severe disease. However, ongoing post-marketing surveillance and formulation-specific safety reporting are necessary due to variations in preterm birth risk that rely on timing and formulation.