MOMI Clinical Core

MOMI 临床核心

• 批准号: 10611522
• 负责人: Andrea Goldberg Edlow
• 金额: $ 48.95万
• 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/10611522
• 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; Diabetes Mellitus; Diphtheria; Enrollment; Feces; Fetal health; Fetus; Future; Gestational Age; Goals; Grant; Hypertension; Immune; Immunity; Immunoglobulin G; Immunologics; Individual; Influenza; Influenza A Virus, H1N1 Subtype; Influenza vaccination; Infrastructure; Innate Immune Response; 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; Recommendation; Research; Research Personnel; Risk; SARS-CoV-2 infection; Sampling; Serum; 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; pregnancy disorder; 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：摘要 该U19的总体目标是阐明妊娠免疫，因为它控制着材料和胎儿健康。一个 在怀孕过程中，关于先天和适应性免疫的知识存在很大的知识差距 以及免疫签名中的扰动，在怀孕的每个三个月中如何表现出来 对母亲和胎儿的风险。怀孕中存在免疫悖论，因为母亲必须忍受半 同种异性胎儿，同时保护自己和胎儿免受致病性挑战。揭示全面 通过怀孕的孕产妇免疫功能无疑会导致对母亲的深入了解 疾病的发病率和死亡率，例如影响力和互联-19，因此开放了新的，以前 无法识别的治疗窗口。预防母体发病率的当前疗法包括疫苗接种， 为母亲和胎儿带来好处。但是，我们从中最大化母校和胎儿的能力 疫苗接种受到限制，这是由于有关母体免疫不断转移性质的知识差异很大 整个妊娠。孕产妇疫苗接种，例如反对影响力的疫苗，提供了增强的免疫力 孕产妇的发病率和季节性影响的死亡率。孕产妇对影响的疫苗接种是普遍的 推荐用于母校福利。对影响力的胎儿益处是一个著名的额外 好处，但不是孕妇疫苗倡导的主要驱动力。相比之下，孕产妇 在没有已知利益的情况下，可以使用疫苗接种对胎儿有直接利益 母亲（例如DPT）。虽然孕产妇疫苗接种均用于产妇和胎儿福利，但缺乏 有关怀孕期间免疫力的知识，以及它如何随胎龄和外部刺激而变化（例如 病毒感染，疫苗接种），极大地阻碍了母亲和胎儿健康的发展。临床核心 尽管主要研究人员的现有生物库以及 获取新的很少和种族多样化的怀孕队列。这些独特的队列将支持我们 提案母亲的“ OMICS”以最大化免疫力（MOMI）。核心将有两个重点 知识上存在巨大的差距：1）利用母亲的现有纵向样本 具有全面的生物群和严格的临床表型和2）的怀孕 接收临床的孕妇的样本表示疫苗为“ Bowosts”（例如SARS-COV-2，流感和 DPT）。这些新焦点将促进对纵向先天和适应性免疫组织化学的首次系统分析 怀孕的人以及母体疫苗接种如何利用或伴随孕妇免疫健康。继续 临床核心的重点将是维持和扩展来自怀孕的大量血液和组织样本 为了解决临床变量的影响，个人并严格表型所有参与者 与免疫扰动有关（例如BMI，妊娠高血压疾病，糖尿病）。