Vaccine effectiveness of the maternal RSVpre-F vaccine against severe disease in infants in Scotland, UK: national population-based case-control and cohort analyses

Evidence before this study

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections (LRTI) in infants and young children globally, contributing significantly to hospitalisations and healthcare burden each year. While most infections are mild, RSV can lead to severe disease in infants, particularly those under six months of age, in preterm infants and in children with underlying medical conditions. Recently, the UK approved use of the Abrysvo® Pre-F RSV (henceforth RSVpre-F) vaccine among pregnant women to protect infants against severe outcomes of RSV, representing a major shift in the public health management of this pathogen. Given that the RSVpre-F vaccine has only been delivered in a small number of countries to date, there are limited studies showing real-world vaccine effectiveness (VE) of RSV vaccines given to pregnant women to protect infants.

We searched PubMed originally on July 1, 2025, then performed a follow-up search on July 29, 2025, using the search terms ((((RSV) OR (respiratory syncytial)) AND (vaccine effectiveness)) AND (maternal)) AND (pregnancy). The literature search was restricted to literature produced between June 21, 2023 (the date that the RSV vaccine was recommended in the USA) and July 29, 2025. There were no language restrictions in our searches. Our searches returned 34 papers. Of these, two were qualitative studies, five were editorials, two were modelling studies, four examined cost-effectiveness of the vaccine, nine were literature reviews, and nine investigated vaccine efficacy rather than effectiveness. Under randomised clinical trial conditions, the reported vaccine efficacy against hospitalisation ranged from 65.5% to 100%.

The remaining three papers from our literature review described RSV maternal VE in Argentina and the UK, using case-control studies similar to our analyses but conducted in selected medical centres rather than across the full population. The first paper by Marc et al. reported VE against RSV-related hospitalisation of 78.6% (95% confidence interval (CI): 62.1-78.9) in those aged 0-3 months and 71.3% (95% CI: 53.5-82.3) in those aged 0-6 months. The second by Gentile et al. reported VE of 78.7% (95% CI: 51.4-90.7) in those aged 0–3 months and 68.2% (95% CI: 33.1-84.9) in those aged 0-6 months. In both studies, RSV vaccine was administered to pregnant women between 32 and 36 weeks of gestation and used multi-centre test negative case-control designs. The final paper by Williams et al., a multi-centre study carried out over Scotland and England, reported a VE of 72% for infants whose mothers were vaccinated more than 14 days before delivery.

Added value of this study

We use a nested case-control methodology to estimate VE against RSV-related hospitalisation among all Scottish infants aged ≤90 days, born between August 12, 2024 and March 31, 2025. Vaccines were given to pregnant women from 28 weeks’ gestation-with a median week of gestion of 30 weeks. This is earlier than the Argentinian studies, where the vaccine was administered between 32-36 weeks, and vaccine efficacy trials, where the median gestational week of vaccination was 31 weeks. Rather than a multi-centre approach, we used population-wide routinely collected clinical data to examine all hospitalisations of infants in Scotland with an RSV positive PCR test and coded with LRTI. Individual-level mother-baby data linked through national clinical, vaccination, and laboratory data systems were used to estimate VE.

Our results showed high population-level VEs, with an 82.9% (95% CI: 75.9–87.8) reduction in RSV-related LRTI hospitalisations among infants ≤90 days whose mothers were vaccinated compared to unvaccinated. From this, we estimated that 228 (95% CI: 197-252) RSV-related LRTI hospitalisations were averted in babies in Scotland across the study period. To test the robustness of findings, we undertook a secondary retrospective matched cohort design, showing a similar estimate of VE against RSV-related LRTI hospitalisations at 81.0% (95% CI: 68.6-88.5). Further, we were able to show that the vaccine was effective against RSV-related LRTI hospitalisations in preterm infants (<37 weeks; 89.2%, 95%CI: 52.2-97.6), and that sub-optimal immunisation (<14 days between vaccination and birth) did not confer protection against hospitalisation (29.6%, 95%CI: −19.6–58.6).

This study represents the first real-world evidence of maternal RSV VE in a national, population-based cohort of pregnant women vaccinated from 28 weeks’ gestation. Further, this study is the first to report the effects of sub-optimal immunisation in infants from mothers who were vaccinated less than two weeks before giving birth, the first to evidence protection for preterm babies, who are typically at greater risk of RSV-related hospitalisations than full term babies, and the first to provide an estimate of RSV-related hospitalisations averted. Our study also uses a separate validation approach using a retrospective matched cohort design to overcome potential bias from unmeasured confounding associated with infant factors.

Implications of all the available evidence

RSV vaccination was effective against LRTI hospitalisations, including in babies born prematurely. In summary, we provide robust evidence of the substantial protection afforded by maternal RSV vaccination offered from 28 weeks’ gestation against RSV-related hospitalisation in infants.