Research Project 1 - The pregnancy ImmunOME

研究项目 1 - 妊娠 ImmunOME

基本信息

批准号：
10611526
负责人：
Andrea Goldberg Edlow
金额：
$ 74.79万
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/10611526
关键词：
Address Adenoviruses Adjuvant Age Antigens Area Atlases Biological Assay Body mass index COVID-19 pandemic COVID-19 vaccination COVID-19 vaccine Cell Separation Cells Cellular Assay Cellular Indexing of Transcriptomes and Epitopes by Sequencing Characteristics Child Chromatin Clinical Collaborations Complex Data Data Analyses Disease Enrollment Ensure Equilibrium Fc Receptor Feces Future Goals High-Throughput Nucleotide Sequencing Human Immune Immune Tolerance Immune response Immune system Immunity Immunologics Immunology In Vitro Infant Infection Inflammation Influenza Infrastructure Innate Immune Response Knowledge Maps Maternal Mortality Maternally-Acquired Immunity Messenger RNA Metabolic Diseases Metagenomics Mothers Peripheral Blood Mononuclear Cell Pertussis Pertussis Vaccine Plasma Population Pregnancy Pregnancy Trimesters Pregnant Women Proliferating 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 Woman Work adaptive immune response antibody transfer booster vaccine cell type cohort data integration data management early pregnancy emerging pathogen experimental study fetal gut microbiome healthy pregnancy high dimensionality in vivo influenza virus vaccine insight maternal immune system 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 COVID-19 大流行彻底改变了我们解读孕产妇免疫规则的能力。关于怀孕期间先天性和适应性免疫反应的知识存在巨大差距以及孕期特异性的母体免疫特征扰动如何在归因中表现出来 COVID-19 疫苗对母婴关系的风险或益处以及孕妇在现实世界中的使用情况。提供了一个独特的机会来定义基线、妊娠期特异性免疫特征，并检查体内干扰后的母体免疫反应从头开始（免疫系统以前从未见过）系统）和召回（增强反应，如流感和百日咳）疫苗在孕产妇免疫最大化组学 (MOMi) 联盟的项目 1 中，我们建议应用多组学方法来深入、全面地捕捉母体免疫的变化我们将分析孕产妇在整个怀孕期间免疫接种前后的反应。产妇疫苗接种前后的血液单核细胞、血浆、胎盘细胞分离物和粪便，使用单细胞 RNA 测序 (scRNA-Seq)，以高通量检测转座酶可及的染色质测序 (scATAC-Seq)、通过测序对转录组和表位进行细胞索引 (scCITE-Seq)、蛋白质组学、代谢组学和宏基因组学，并通过数据管理和集成所有数据分析核心 (DMAC) 与项目 2 合作，最终目标是定义母体免疫力。在正常基线和恶性状态下纵向跨越妊娠三个月，以建立最母胎先天性和适应性免疫分析的综合妊娠免疫图谱我们将研究细胞转录组、微生物组、代谢组和蛋白质组如何变化。怀孕过程，以及如何修改它们以响应不同的疫苗平台（mRNA、腺病毒、佐剂蛋白）和类型（从头到回忆），提供了一个独特的机会来描述母体这张详细的妊娠免疫图谱将产生至关重要的免疫反应。数据在这个不寻常且未被充分研究的人类领域打开了以前未被认识的治疗窗口免疫学。