MOMI Clinical Core

MOMI 临床核心

• 批准号: 10420108
• 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/10420108
• 关键词: 2019-nCoV; Address; Advocacy; Allogenic; Biological Specimen Banks; Blood; Blood Banks; Blood specimen; Body mass index; COVID-19; COVID-19 vaccination; COVID-19 vaccine; Catalogs; Clinical; Clinical Data; Collection; Data; Data Analyses; Databases; Diphtheria; Enrollment; Feces; Fetal health; Fetus; Future; Gestational Age; Gestational Diabetes; Goals; Grant; Hypertension; Immune; Immunity; Immunoglobulin G; Immunologics; Individual; Influenza; Influenza A Virus, H1N1 Subtype; Influenza vaccination; Infrastructure; Knowledge; Lead; Maternal Health; Maternal Mortality; Maternal antibody; Maternally-Acquired Immunity; Metadata; Mothers; Natural Immunity; Nature; Participant; Pathogenicity; Peripheral Blood Mononuclear Cell; Pertussis; Phenotype; Plasma; Pregnancy; Pregnancy Trimesters; Prospective cohort; Research; Research Personnel; Risk; SARS-CoV-2 infection; Sampling; Specimen; Stimulus; Tetanus; Therapeutic; Third Pregnancy Trimester; Tissue Banks; Tissue Sample; Vaccination; Vaccines; Virus Diseases; Work; adaptive immune response; adaptive immunity; biobank; clinical phenotype; clinically relevant; cohort; data management; ethnic diversity; fetal; flu; immune health; longitudinal analysis; maternal morbidity; maternal vaccination; neonate; pandemic disease; placental transfer; pregnant; prepregnancy; prevent; racial diversity; sample collection; seasonal influenza

Clinical Core: Summary The overall goal of this U19 is to elucidate the pregnancy immunome as it governs maternal and fetal health. A large gap in knowledge exists regarding innate and adaptive immune responses over the course of pregnancy and how perturbations in the immunological signature, in each trimester of pregnancy, manifest in attributable risk to the mother and fetus. An immune paradox exists in pregnancy, as the mother must tolerate a semi- allogenic fetus while protecting herself and the fetus from pathogenic challenge. Revealing the comprehensive function of maternal immunity through pregnancy will undoubtedly lead to advanced understanding of maternal morbidity and mortality from illness such as influenza and COVID-19 and, as such, open new, previously unrecognized, therapeutic windows. Current therapies to prevent maternal morbidity include vaccinations, which afford benefit to both the mother and fetus. Yet, our ability to maximize maternal and fetal benefit from vaccination is limited due to a large gap in knowledge regarding the ever-shifting nature of maternal immunity across gestation. Maternal vaccination, such as that against influenza, provides enhanced immunity to prevent maternal morbidity and mortality from seasonal influenza. Maternal vaccination against influenza is universally recommended for maternal benefit. Fetal benefit from maternal vaccination against influenza is a noted additional benefit but is not the primary driver of vaccine advocacy among pregnant individuals. In contrast, maternal vaccination can be employed to have a direct benefit to the fetus in the absence of known benefit to the mother (e.g. DPT). While maternal vaccination is utilized for both maternal and fetal benefit, the lack of knowledge regarding immunity during pregnancy, and how it shifts with gestational age and external stimuli (e.g. viral infection, vaccination), greatly impedes needed advancement in maternal and fetal health. The clinical core will support all the projects in this proposal though existing biobanks from key investigators, as well as the acquisition of a new racially and ethnically diverse pregnancy cohort. These unique cohorts will support our proposal Maternal ‘Omics to Maximize Immunity (MOMi). The core will have two focuses for which there are tremendous existing gaps in knowledge: 1) to leverage existing longitudinal samples from mothers across pregnancy with comprehensive biobanking and rigorous clinical phenotyping and 2) to collect longitudinal samples from pregnant individuals receiving clinically indicated vaccines as “boosts” (e.g. SARS-CoV-2, Flu, and DPT). These new foci will facilitate the first systematic analyses of longitudinal innate and adaptive immunity in pregnant individuals and how maternal vaccinations leverage or perturbs pregnant immune health. A continued focus of the Clinical Core will be to maintain and expand a large bank of blood and tissue samples from pregnant individuals and to rigorously phenotype all participants, in order to address the impact of clinical variables associated with immune perturbations (e.g. BMI, hypertensive disorders of pregnancy, diabetes).

临床核心：总结 该 U19 的总体目标是阐明妊娠免疫组，因为它控制着孕产妇和胎儿的健康。一个 关于妊娠期间先天性和适应性免疫反应的知识存在巨大差距 以及在怀孕的每个三个月中免疫学特征的扰动如何表现在归因 对母亲和胎儿的风险。怀孕期间存在免疫悖论，因为母亲必须忍受半免疫 同种异体胎儿，同时保护自己和胎儿免受病原体挑战。全面揭示 怀孕期间母体免疫力的功能无疑会导致对母体的进一步了解 流感和 COVID-19 等疾病的发病率和死亡率，因此，打开了新的、以前的 未被识别的治疗窗口。目前预防孕产妇发病的疗法包括疫苗接种， 对母亲和胎儿都有利。然而，我们有能力最大限度地提高母亲和胎儿的利益 由于对孕产妇免疫力不断变化的性质认识存在巨大差距，疫苗接种受到限制 跨妊娠期。母亲接种疫苗，例如流感疫苗，可以增强免疫力，预防 季节性流感导致的孕产妇发病率和死亡率。母亲普遍接种流感疫苗 推荐用于母亲利益。母亲接种流感疫苗对胎儿的好处是一个值得注意的额外因素 好处，但不是在孕妇中宣传疫苗的主要驱动力。相比之下，母亲 在对胎儿没有已知益处的情况下，可以采用疫苗接种来对胎儿产生直接益处。 母亲（例如 DPT）。虽然孕产妇疫苗接种对孕产妇和胎儿都有好处，但缺乏 有关怀孕期间免疫力的知识，以及免疫力如何随胎龄和外部刺激（例如，怀孕）而变化的知识 病毒感染、疫苗接种），极大地阻碍了孕产妇和胎儿健康所需的进步。临床核心 将通过主要研究人员的现有生物库以及 获得一个新的种族和民族多样化的怀孕队列。这些独特的群体将支持我们 提案“最大化免疫力的母亲组学”（MOMi）。核心将有两个焦点 现有的知识差距是巨大的：1）利用来自不同国家母亲的现有纵向样本 通过全面的生物样本库和严格的临床表型分析来确定妊娠，并 2) 收集纵向数据 接受临床指示疫苗“加强”（例如 SARS-CoV-2、流感和 DPT）。这些新的焦点将有助于对纵向先天免疫和适应性免疫进行首次系统分析。 怀孕个体以及孕产妇疫苗接种如何影响或扰乱怀孕的免疫健康。继续 临床核心的重点将是维护和扩大大量孕妇的血液和组织样本库 个体并对所有参与者进行严格的表型分析，以解决临床变量的影响 与免疫紊乱有关（例如体重指数、妊娠高血压疾病、糖尿病）。