Background and Disease Burden
Respiratory syncytial virus (RSV) is recognized as the leading pathogen responsible for acute lower respiratory infections (ALRI) in infants younger than six months globally. These infections contribute significantly to infant morbidity and hospitalisation rates worldwide, posing a persistent public health challenge. Despite decades of research, preventive interventions to protect the most vulnerable infants have remained limited.
In response, in late summer 2024, the UK introduced a maternal bivalent RSV prefusion F (RSVpreF) vaccine, targeting pregnant women at or beyond 28 weeks gestation. The vaccine aims to elicit maternal antibody responses that are transferred across the placenta to confer passive immunity on newborns during the critical first months of life, when RSV disease burden is highest.
Study Design
To evaluate the real-world effectiveness of this vaccine, the study by Williams et al. employed a multicentre, test-negative, case-control design involving 30 hospital sites across England and Scotland. Eligible infants included those admitted with acute lower respiratory infections born after maternal vaccination program initiation dates (August 12, 2024 in Scotland and September 1, 2024 in England).
Between September 30, 2024, and January 20, 2025, 537 mother-infant pairs were recruited, 391 of whom tested RSV-positive (cases) and 146 RSV-negative (controls). Data incorporated patient and public involvement from parent groups in protocol design, enhancing the study’s patient-centered approach.
The primary outcome was hospital admission due to RSV-associated ALRI in infants. Vaccine effectiveness was assessed using conditional logistic regression, adjusting for confounders including study site, calendar month, infant age, prematurity, and sex.
Key Findings
The median age of RSV-positive infants was approximately 1.63 months, emphasizing the vulnerability of very young infants. Among the RSV-positive cases, only 19% of mothers had received RSVpreF vaccination before delivery compared with 41% in RSV-negative controls, indicating a protective effect of maternal immunization.
Adjusted vaccine effectiveness against infant hospitalisation was 58% (95% CI 28-75) for any maternal vaccination before delivery. Remarkably, effectiveness rose to 72% (95% CI 48-85) when mothers were vaccinated more than 14 days prior to delivery, highlighting the importance of timely vaccination for optimal antibody transfer.
The findings demonstrate a tangible reduction in RSV-associated hospitalisation risk comparable to that observed in earlier clinical trials. The high protective efficacy validates maternal RSVpreF vaccination as a critical preventive strategy to mitigate severe RSV disease burdens in infants during early infancy.
Expert Commentary
These results are among the first to confirm in a real-world setting the substantial infant protection afforded by maternal vaccination with RSVpreF in the UK. They align with the biological plausibility of transplacental antibody transfer providing early-life immunity against RSV. The test-negative design strengthens inference by controlling for health-seeking behavior and access to care.
Limitations include the relatively short follow-up period and the limited ethnic diversity of the cohort, predominantly White. Future studies should explore longer-term outcomes and efficacy in diverse populations. Additionally, integrating maternal vaccination into routine antenatal care pathways remains essential to maximise coverage and population-level impact.
Conclusion
This multicentre UK study delivers robust evidence supporting maternal bivalent prefusion F RSV vaccination as an effective intervention to reduce hospitalisation for RSV-associated ALRI in infants, with up to 72% reduction when administered at least 14 days prior to delivery. The findings endorse widespread implementation to improve infant respiratory health outcomes and reduce healthcare burdens associated with RSV in early infancy.
Clinicians and policymakers should prioritize maternal RSVpreF vaccination as part of antenatal care, with ongoing surveillance to monitor effectiveness and safety. This real-world data bridge the gap from clinical trials to effective population health strategies addressing a critical neonatal infectious disease.
References
Williams TC, Marlow R, Cunningham S, Drysdale SB, Groves HE, Hunt S, Iskander D, Liu X, Lyttle MD, Mpamhanga CD, O’Hagan S, Waterfield T, Roland D; PERUKI & BronchStart Collaboration. Bivalent prefusion F vaccination in pregnancy and respiratory syncytial virus hospitalisation in infants in the UK: results of a multicentre, test-negative, case-control study. Lancet Child Adolesc Health. 2025 Sep;9(9):655-662. doi: 10.1016/S2352-4642(25)00155-5. Epub 2025 Jul 18. PMID: 40690922.