PROJECT SUMMARY/ABSTRACT Pregnant individuals are more likely to require invasive mechanical ventilation or die from complications related to coronavirus disease 2019 (COVID-19) than non-pregnant women. COVID-19 vaccination in pregnancy can prevent the consequences of infection for the mother and provide passive immunity to newborns through placental transfer of vaccine-induced antibodies. The maternal immune system undergoes adaptive changes during pregnancy characterized by both active suppression of immune responses against the developing pregnancy and pro-inflammatory signals to promote healthy implantation and initiate labor. The central hypothesis is that the adaptive immunologic changes in pregnancy lead to differences in the development of vaccine-induced immunity depending on the gestational age at vaccination and/or the vaccine platform used. The overall objective of this proposal is to address important knowledge gaps including limited information regarding cellular immune responses following maternal vaccination, immune responses after vaccination in early pregnancy, and comparison of immunogenicity across different vaccine platforms. The research proposed is innovative because we will use a comprehensive immune profiling approach to quantify functional cellular and antibody responses in order to define the COVID-19 vaccine type and timing that optimizes robust and durable maternal vaccine-induced immunity (Aim 1) and neonatal passive immunity from placental transfer of viral neutralizing antibody (Aim 2). The proposed research is significant because it is expected to provide data to inform clinical recommendations for COVID-19 vaccines in pregnancy to improve maternal and neonatal outcomes. The long-term goal will be to provide preliminary data for a larger study evaluating vaccine efficacy for pregnant individuals and their neonates. The knowledge provided by this proposal will also inform future vaccine development for other important and emerging pathogens in pregnancy.