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Research Project 1 - The pregnancy ImmunOME

研究项目 1 - 妊娠 ImmunOME

基本信息

批准号：
10420109
负责人：
Andrea Goldberg Edlow
金额：
$ 47.08万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-19 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10420109
关键词：
Address Adenoviruses Adjuvant Age Antigens Area Atlases Biological Assay Body mass index COVID-19 pandemic COVID-19 vaccination COVID-19 vaccine Cells Cellular Assay Cellular Indexing of Transcriptomes and Epitopes by Sequencing Characteristics Chromatin Clinical Collaborations Complex Data Data Analyses Disease Enrollment Ensure Equilibrium Fc Receptor Feces Future Goals High-Throughput Nucleotide Sequencing Human Immune Immune response Immune system Immunity Immunologics Immunology In Vitro Infant Infection Inflammation Influenza Infrastructure Knowledge Maps Maternally-Acquired Immunity Messenger RNA Metabolic Diseases Metagenomics Mothers Peripheral Blood Mononuclear Cell Pertussis Pertussis Vaccine Plasma Population Pregnancy Pregnancy Trimesters Pregnant Women Proteins Proteome Proteomics Recording of previous events Research Project Grants Resolution Risk SARS-CoV-2 negative Sampling Shapes Shotguns Systems Biology Therapeutic Time Transposase Vaccinated Vaccination Vaccine Design Vaccines Work adaptive immune response antibody transfer booster vaccine cohort data management early pregnancy emerging pathogen experimental study fetal gut microbiome healthy pregnancy high dimensionality in vivo influenza virus vaccine insight maternal vaccination metabolome metabolomics metagenomic sequencing microbial microbiome multidisciplinary neonate next generation novel pandemic disease pathogen placental transfer prospective receptor expression response sex single-cell RNA sequencing therapeutic development transcriptome vaccine development vaccine platform vaccine response vaccine strategy

项目摘要

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.

项目1：总结