Research Project 1 - The pregnancy ImmunOME

研究项目 1 - 妊娠 ImmunOME

• 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
• 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

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的大流行彻底改变了我们解码产妇免疫规则的能力。有一个 在怀孕过程中了解先天和适应性免疫的差距很大 以及孕妇特定的母体免疫签名中的特异性扰动如何归因于 风险或受益于母亲二元。 Covid-19疫苗及其实际使用孕妇 提供一个独特的机会来定义基线，孕妇特定的免疫特征，并检查 孕产妇免疫反应与两者的体内扰动后（从未被免疫见到 系统）和召回（诸如影响力和百日咳之类的增强反应） 怀孕。在孕产妇的项目1中，在最大化免疫力（MOMI）财团中，我们建议 采用多种方法的方法来深入，全面地捕获母体免疫的转变 孕产妇免疫之前和之后的反应。我们将介绍孕妇外围 血液单核细胞，血浆，局部细胞分离株和粪便前后的粪便，母亲疫苗接种， 使用单细胞RNA-SEQ（SCRNA-SEQ），用于转座酶可访问的染色质的测定 测序（SCATAC-SEQ），通过测序（SCCITE-SEQ）的转录组和表位的细胞索引， 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，最终目标是定义物质免疫力 在正常基线和疫苗接种状态下，在怀孕的三个纵向上，以建造最多 跨母校的综合怀孕免疫和适应性免疫分析 二元。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 怀孕过程，以及如何根据不同的疫苗平台进行修饰（mRNA，腺病毒， 调整后的蛋白质）和类型（从头进行回忆），提供了一个独特的机会来介绍母体 免疫反应以前所未有的分辨率。这张怀孕免疫的详细地图将产生关键 在这个不寻常且知识的人类领域中打开先前未知的治疗窗口的数据 免疫学。