Study protocol: Effectiveness of the maternal RSVpreF vaccine by virus type

Respiratory syncytial virus (RSV) is a virus with two antigenic types, A and B, that cause significant morbidity and mortality in infants globally. A recently developed maternal vaccination based on the prefusion F protein ("RSVpreF") could have a significant impact on disease burden, if introduced globally. Whether or not the effectiveness of this vaccine is affected by circulating viral genomic variability is currently unknown.

To examine whether the vaccine effectiveness of maternal RSVpreF administration in preventing hospitalisation in infants is affected by RSV type or lineage.

We will conduct whole genome sequencing of RSV positive samples from infants hospitalised with acute lower respiratory tract infection (ALRI) in the 2024-2025 winter season, at multiple hospitals in England and Scotland, to calculate the relative vaccine effectiveness (rVE) of maternal RSVpreF vaccination by virus type (RSV-A and RSV-B). rVE will be calculated using a case control logistic regression with adjustment by infant age and admission date; sex, socioeconomic status and hospital location will be included as potential confounders if they are associated with a >3% change in rVE. We will also perform a test negative design to examine the VE for RSV-A and RSV-B separately, using RSV-negative controls from hospitals where cases were admitted. Finally, we will compare viral lineages in vaccinated versus unvaccinated infants.

Our study will identify whether currently circulating RSV genomic variability impacts on rVE. Confirmation of the null hypothesis - that there is no impact of viral genomic variability on rVE - will provide reassurance to policymakers and public health bodies as RSVpreF is rolled out globally. Conversely, an association between RSV type or lineage and decreased vaccine effectiveness will highlight the need for the enhanced comprehensive national and global molecular surveillance of RSV.