Clinical Core: Summary The overall goal of this U19 is to elucidate the pregnancy immunome as it governs maternal and fetal health. A large gap in knowledge exists regarding innate and adaptive immune responses over the course of pregnancy and how perturbations in the immunological signature, in each trimester of pregnancy, manifest in attributable risk to the mother and fetus. An immune paradox exists in pregnancy, as the mother must tolerate a semi- allogenic fetus while protecting herself and the fetus from pathogenic challenge. Revealing the comprehensive function of maternal immunity through pregnancy will undoubtedly lead to advanced understanding of maternal morbidity and mortality from illness such as influenza and COVID-19 and, as such, open new, previously unrecognized, therapeutic windows. Current therapies to prevent maternal morbidity include vaccinations, which afford benefit to both the mother and fetus. Yet, our ability to maximize maternal and fetal benefit from vaccination is limited due to a large gap in knowledge regarding the ever-shifting nature of maternal immunity across gestation. Maternal vaccination, such as that against influenza, provides enhanced immunity to prevent maternal morbidity and mortality from seasonal influenza. Maternal vaccination against influenza is universally recommended for maternal benefit. Fetal benefit from maternal vaccination against influenza is a noted additional benefit but is not the primary driver of vaccine advocacy among pregnant individuals. In contrast, maternal vaccination can be employed to have a direct benefit to the fetus in the absence of known benefit to the mother (e.g. DPT). While maternal vaccination is utilized for both maternal and fetal benefit, the lack of knowledge regarding immunity during pregnancy, and how it shifts with gestational age and external stimuli (e.g. viral infection, vaccination), greatly impedes needed advancement in maternal and fetal health. The clinical core will support all the projects in this proposal though existing biobanks from key investigators, as well as the acquisition of a new racially and ethnically diverse pregnancy cohort. These unique cohorts will support our proposal Maternal ‘Omics to Maximize Immunity (MOMi). The core will have two focuses for which there are tremendous existing gaps in knowledge: 1) to leverage existing longitudinal samples from mothers across pregnancy with comprehensive biobanking and rigorous clinical phenotyping and 2) to collect longitudinal samples from pregnant individuals receiving clinically indicated vaccines as “boosts” (e.g. SARS-CoV-2, Flu, and DPT). These new foci will facilitate the first systematic analyses of longitudinal innate and adaptive immunity in pregnant individuals and how maternal vaccinations leverage or perturbs pregnant immune health. A continued focus of the Clinical Core will be to maintain and expand a large bank of blood and tissue samples from pregnant i...