CAUSAL-RSV: A study protocol for a causal mediation analysis of RSV vaccine effects in infants using real-world data

1.Respiratory syncytial virus (RSV) contributes to substantial morbidity and mortality in young children each year. In 2023, two new prevention products were licensed and recommended in the United States (US), including a prefusion F protein subunit vaccine (RSVpreF) administered during pregnancy and a long-acting monoclonal antibody (mAb) administered in infants. Although post-licensure real-world studies support the effectiveness of RSVpreF vaccine during pregnancy, existing studies have been conducted in settings where only RSVpreF vaccine is available. The real-world effectiveness of RSVpreF vaccine in settings where both RSVpreF vaccine and mAbs are available is not yet well understood. The goal of this study is to estimate the real-world effectiveness of the RSVpreF vaccine against severe infant RSV by applying causal mediation analysis with receipt of mAbs as a mediating variable. Using a national cohort of mother-infant dyads with the Optum Labs Data Warehouse (OLDW), we will model vaccine and mAb effects in a longitudinal cohort spanning the 2023-24, 2024-25, and 2025-26 RSV seasons. Results will be used to better understand the total effect of RSVpreF vaccination when it is used as one component within a hybrid infant RSV prevention program.