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

## TL;DR

This study will determine if a maternal RSV vaccine is equally effective against two RSV types (A and B) in infants.

## Contribution

The study investigates whether RSV genomic variability affects the effectiveness of maternal RSVpreF vaccination.

## Key findings

- The study will calculate relative vaccine effectiveness (rVE) by RSV type using genome sequencing and logistic regression.
- It will compare viral lineages in vaccinated and unvaccinated infants to detect potential effectiveness differences.
- Findings will inform global RSV vaccination strategies and surveillance needs.

## Abstract

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.

Respiratory syncytial virus, often shortened to be called RSV, is a common virus that can cause severe infections in children. In babies, RSV is more likely to cause severe disease, and RSV disease is a common cause of hospital admission in this group. Recently, an effective vaccine against RSV, given to pregnant women to protect their babies after birth, has been introduced in some countries, including England and Scotland. There are two types of RSV, called RSV-A and RSV-B, which circulate in communities every year; whether the maternal vaccine antibodies transferred to the women’s infants are equally protective against both types isn’t known. We will conduct a study to determine whether the maternal vaccine is equally effective against RSV-A and RSV-B.

The World Health Organization has recommended that all babies should be protected against RSV infection, and maternal RSV vaccination is likely to be introduced in many countries across the world. If the vaccine is less effective against a particular RSV type, it will be important to monitor the circulation of that RSV type, and consider changing the vaccination so that it is more effective.

RSV infection causes a significant global burden of disease in babies, which could be reduced by maternal vaccination. Our study will find out whether the type of RSV that a baby is infected with makes it more or less likely for the maternal vaccine to work.