Glasgow Maternal and Infant RSV Immunity Study (GLAMIRIS)

Respiratory syncytial virus (RSV) is the most common cause of respiratory infection in children and a major cause of infant deaths worldwide. New RSV immunisation strategies should reduce hospital admissions and save lives. The UK has recently introduced RSV vaccination in pregnancy from 28 weeks. Other countries have introduced neonatal immunisation with nirsevimab, a man-made RSV antibody. Both strategies aim to protect infants in early life. Maternal immunisation protects infants by transfer of maternal antibody through the placenta. Preterm birth and maternal conditions affecting the placenta may lead to reduced transplacental antibody transfer, potentially reducing maternal vaccine effectiveness. Maternal infections, such as HIV and malaria, cause placental inflammation and abnormal placental development, and are known risk factors for reduced transplacental antibody transfer. It is unclear whether other conditions, such as smoking, obesity and diabetes, which also cause abnormal placental development, have a similar effect. Rates of obesity and diabetes in pregnancy are high and increasing in the UK. These conditions also increase the risk of preterm birth and are associated with socio-economic deprivation. Preterm birth and deprivation are also known to increase the risk of infant RSV disease. If these common maternal conditions do reduce transplacental antibody transfer, this may mean that maternal RSV vaccination is more likely to fail those most in need of protection. It is important to determine this, given an alternative immunisation strategy is available. We aim to determine the relationship between maternal risk factors for placental abnormalities, placental antibody transfer, placental inflammation and infant risk of RSV disease. We will establish a mother-infant data cohort from all births in Greater Glasgow & Clyde over 2 years (approximately 26,000 mother-infant pairs). Within this cohort, we will collect infant and maternal blood from the umbilical cord and placenta of 6000 mother-infant pairs. Data and selected samples will be used for four integrated studies: Study 1: A cohort study to establish risk factors for maternal RSV vaccine failure. Maternal and infant risk factors will be compared in vaccine-exposed infants with and without hospitalised RSV <6 months of age. Study 2: A case-control study to determine whether RSV antibody levels at birth predict the risk of infant RSV. This will compare RSV antibodies in date-of-birth matched infants with and without hospitalised RSV <6 months of age. Study 3: A case-control study to determine whether maternal risk factors (obesity, diabetes, smoking) are associated with reduced transplacental antibody transfer. This will compare RSV antibodies in 100 mother-infant pairs in each of the three risk groups to 200 pairs without these risks. Study 4: A case-control study to explore placental inflammation and its relationship to transplacental antibody transfer in 50 mother-infant pairs in each of 3 maternal risk groups (obesity, diabetes and smoking) compared to 100 mother-infant pairs without these conditions. This study will also collect placental tissue. Identifying risk factors for maternal RSV vaccine failure will help countries choose the best RSV prevention strategy for their population. Infants at higher risk could benefit from targeted neonatal immunisation strategies. Determining a level of RSV antibody at birth that protects against early RSV disease could help inform future vaccine development. Determining the relationship between placental inflammation and antibody transfer will improve our understanding of early infant immunity. This is important not just to prevent RSV, but also to prevent other infections in infants.