Real-World Effectiveness of Maternal RSV Vaccination - PROJECT SUMMARY Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection (LRTI) in infants, contributing to 33 million episodes of RSV-associated LRTIs and 101,400 deaths in children each year. There are currently no antiviral therapies or other effective treatments to manage RSV illness, making prevention optimal for controlling RSV. In 2023, the world’s first RSV vaccine was licensed and recommended for administration during pregnancy between the 32nd and 36th week of pregnancy. Prelicensure clinical trial data to support the introduction of the vaccine showed that when given between 24 and 36 weeks of pregnancy, the vaccine is 57% effective in preventing RSV-associated LRTIs among infants <3 months old. Given its brief period of use, the performance of the RSV vaccine outside of the prelicensure clinical trials has not yet been described. Several important factors could impact the performance of the RSV vaccine in the real- world setting. First, around the same time that the RSV vaccine became available, nirsevimab was licensed and recommended in the US. Nirsevimab is a monoclonal antibody that is currently recommended as a single dose for infants <8m. In settings like the US, where both RSV vaccine and nirsevimab are available to parents, real-world vaccine evaluation will need to account for whether nirsevimab was received during infancy. Failure to do so may result in biased and incomplete understanding of the RSV vaccine’s performance. Second, the gestational age at vaccination recommended by US policymakers is later in pregnancy (32-36 weeks) than the gestational age at vaccination in the prelicensure clinical trials (26-36 weeks). Given maternal antibody transfer is maximal when administered ~4 weeks before delivery, this may adversely affect the real-world performance of the RSV vaccine. Finally, prelicensure clinical trials specifically excluded pregnant people with a pregnancy complication, who are at higher risk of preterm birth, and the trials were not large enough to measure vaccine effects among preterm infants. Infants born premature are at higher risk of severe RSV-associated LRTIs compared to term infants and potentially stand to benefit more from RSV vaccination. Despite this, the effectiveness of RSV vaccine has not yet been investigated among these infants. Post-licensure real-world studies will be pivotal in understanding how the RSV vaccine performs in the context of nirsevimab availability, when administered during the later gestational period (32 to 36 weeks), and among patient subgroups. Using national linked administrative health data spanning three RSV seasons for 117,000 mother-infant pairs, the proposed project will (1) estimate the total real-world effectiveness of the maternal RSV vaccine, and (2) quantify any differences in the effectiveness by the gestational age at vaccination and by high-risk group. This comprehensive, real-world study will address critical gaps left unanswered by prelicensure clinical trials and provide real-world evidence to support RSV vaccine policies in the US and internationally.
