Serological and functional impact of COVID-19 vaccination on the maternal fetal unit and infant immunity

PROJECT SUMMARY As COVID-19 pandemic continues with the evolution of new strains, we acknowledge the groundwork that has been done evaluating maternal immunity following COVID-19 vaccine or disease exposure in pregnancy, and passive transmission of antibodies in cord blood and breastmilk. There remains a significant knowledge gap at this time relating to first, the impact of booster vaccination on maternal immunity in pregnancy and lactation taking into consideration new strains, and second an understanding of the strength and durability of passively acquired infant immunity through evaluation of infant serology following maternal vaccination in pregnancy or breastfeeding. This knowledge gap has become even more significant in light of the recently started widespread administration of COVID vaccines and now booster doses to pregnant and breastfeeding women and new virulent strains. The impact of COVID-19 vaccination on the maternal-fetal unit needs to be assessed by profiling maternal serologic and immunologic response to vaccination during pregnancy and post partum, and expanding on assessment of breastmilk and cordblood with infant serological studies as well. We propose a multi arm cohort study to carry out a comprehensive evaluation of the impact of COVID-19 booster dose, initial vaccine, and COVID-19 disease on the maternal fetal unit and post-natal infant immunity. This immunoprofiling effort will provide a valuable characterization of humorally mediated immunity in both mother and infant that that can guide clinical vaccine trials and protocols in pregnancy, identify potential neonatal benefits from passive immunity, and inform timing of infant vaccination. The COVID-19 pandemic has prompted the rapid initiation of immunoprofiling studies, but ours is unique: 1) Unlike studies to date we will evaluate longitudinal infant immunity to examine the functional immunity gained from maternal vaccine exposures 2) We are building on an existing cohort of pregnant and lactating women exposed to COVID-19 disease and an initial mRNA vaccine course, as well as banked control samples, to allow for multiple comparison in evaluating immune correlates of vaccine/booster in pregnancy or lactation 3) by using highly dose-sparing, multiplex electroluminescence-based assays, it will characterize a wide range of antibody characteristics of SARS-CoV2 infection and vaccination to characterize the change in serological and functional SARS CoV2 immune profile in mother and neonate following COVID- 19 vaccine and booster exposure 4) by assessing paired maternal, cordblood, breastmilk, and infant blood we will study the role of timing of exposure and maternal on long term neonatal and infant functional immunity; 5) we will use machine-learning to identify predictive correlates of SARS-CoV2 immunity that could help guide vaccine research to maximize maternal and neonatal immunity.