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：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。有一个 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 对母胎二元体的风险或益处。 COVID-19 疫苗及其孕妇的实际使用情况 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（免疫系统从未见过） 系统）和召回（增强反应，如流感和百日咳）疫苗 怀孕。在孕产妇‘最大化免疫组学 (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 孕期母亲免疫接种前后的反应。我们将剖析产妇外围设备 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-Seq (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 在正常基线和疫苗接种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 二人组。我们将研究细胞转录组、微生物组、代谢组和蛋白质组如何随时间变化 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 免疫反应具有前所未有的分辨率。这张详细的妊娠免疫图谱将产生关键的影响 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。