Research Project 1 - The pregnancy ImmunOME

Project 1: Summary The COVID-19 pandemic has revolutionized our ability to decode the rules of maternal immunity. There is a significant gap in knowledge regarding innate and adaptive immune responses over the course of pregnancy and how trimester-specific perturbations in the maternal immunological signature might manifest in attributable risk or benefit to the maternal-fetal dyad. The COVID-19 vaccines and their real-world use by pregnant women present a unique opportunity to define the baseline, trimester-specific immune signature, and to examine the maternal immune response after in vivo perturbation with both de novo (never before seen by the immune system) and recall (boosted responses such as influenza and pertussis) vaccines across the trimesters of pregnancy. In Project 1 in the Maternal 'Omics to Maximize Immunity (MOMi) consortium, we propose to apply a multi-'OMICs approach to deeply and comprehensively capture shifts in the maternal immune response before and after maternal immunization across pregnancy. We will profile maternal peripheral blood mononuclear cells, plasma, placental cell isolates, and stool from pre- and post-maternal vaccination, using single cell RNA-Seq (scRNA-Seq), Assay for Transposase-Accessible Chromatin with high-throughput sequencing (scATAC-Seq), Cellular Indexing of Transcriptomes and Epitopes by Sequencing (scCITE-Seq), proteomics, metabolomics, and metagenomics, and integrate all data through the Data Management and Analysis Core (DMAC). In collaboration with Project 2, the ultimate goal is to define maternal immunity longitudinally across pregnancy trimesters in the normal baseline and vaccinated state, in order to build the most comprehensive Pregnancy Immune Atlas of innate and adaptive immune profiling across the maternal-fetal dyad. We will examine how the cellular transcriptome, microbiome, metabolome, and proteome shifts over the course of pregnancy, and how they are modified in response to different vaccine platforms (mRNA, adenovirus, adjuvanted protein) and types (de novo versus recall), providing a unique opportunity to profile the maternal immune response with unprecedented resolution. This detailed map of pregnancy immunity will generate critical data to open previously unrecognized therapeutic windows in this unusual and understudied area of human immunology.