Research Project 1 - The pregnancy ImmunOME

研究项目 1 - 妊娠 ImmunOME

• 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
• 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

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：摘要 COVID-19大流行彻底改变了我们解读母体免疫规则的能力。有一个 在怀孕过程中对先天性和适应性免疫反应的认识存在重大差距 以及母体免疫特征中的三个月特异性扰动如何表现为可归因于 对母胎二分体的风险或益处。COVID-19疫苗及其在孕妇中的实际使用 提供了一个独特的机会，以确定基线，孕期特异性免疫签名，并检查 母体免疫应答后，在体内扰动与从头（从来没有见过的免疫反应， 系统）和召回（加强反应，如流感和百日咳）疫苗在整个孕期 怀孕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OMIC方法，深入全面地捕捉母体免疫的变化， 在整个怀孕期间，母亲免疫接种前后的反应。我们将分析母体外周血 血液单核细胞、血浆、胎盘细胞分离物和母体接种前后的粪便， 使用单细胞RNA-Seq（scRNA-Seq），高通量测定转座酶可降解染色质 测序（scATAC-Seq），通过测序的转录组和表位的细胞索引（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 分析核心（DMAC）。与项目2合作，最终目标是确定母体免疫力 在正常基线和接种疫苗状态下，在妊娠三个月期间纵向观察，以建立最大的 全面的妊娠免疫图谱，涵盖母胎先天性和适应性免疫谱 二分体我们将研究细胞转录组、微生物组、代谢组和蛋白质组如何在细胞周期中发生变化。 妊娠过程，以及它们如何响应不同的疫苗平台（mRNA，腺病毒， 佐剂蛋白）和类型（从头与回忆），提供了一个独特的机会，以概况孕产妇 免疫反应，前所未有的分辨率。这张详细的妊娠免疫图将产生关键的 数据打开了以前未被认识的治疗窗口，在这个不寻常的和研究不足的领域，人类 免疫学