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：综述 这本U19的总体目标是阐明怀孕免疫组，因为它管理母婴健康。一个 关于怀孕期间的先天免疫反应和获得性免疫反应的知识存在很大差距 以及在怀孕的每三个月中，免疫标志的扰动如何在可归因性中表现出来 对母亲和胎儿的风险。一种免疫悖论存在于怀孕期间，因为母亲必须忍受半耐受 在保护自己和胎儿免受致病挑战的同时，同种异体胎儿。揭示全面的 孕期母体免疫功能的发挥，无疑会加深对母体免疫功能的认识。 流感和新冠肺炎等疾病的发病率和死亡率，因此，以前打开了新的 无法辨认的治疗窗口。目前预防孕产妇发病的疗法包括接种疫苗，这是 对母亲和胎儿都有好处。然而，我们能够最大限度地从母体和胎儿受益 由于对母体免疫的不断变化的性质的认识存在很大差距，疫苗接种受到限制 在怀孕期间。孕妇接种疫苗，如针对流感的疫苗，可增强免疫力，防止 季节性流感的孕产妇发病率和死亡率。孕妇接种流感疫苗是普遍存在的 建议用于产妇福利。孕妇接种流感疫苗对胎儿的好处是一个值得注意的额外因素 对孕妇有益，但不是倡导接种疫苗的主要推动力。相比之下，母体 在不知道对胎儿有好处的情况下，可以使用疫苗接种对胎儿有直接好处 母亲(例如DPT)。虽然孕妇接种疫苗对产妇和胎儿都有好处，但缺乏 关于孕期免疫的知识，以及免疫如何随胎龄和外界刺激而变化(例如 病毒感染、疫苗接种)，极大地阻碍了在孕产妇和胎儿健康方面取得必要进展。临床核心 将通过来自主要调查人员的现有生物库以及 获得一个新的种族和人种多样化的怀孕队列。这些独特的群体将支持我们的 建议母体运动以最大限度地提高免疫力(MOMI)。核心将有两个重点，即 在知识方面存在巨大的差距：1)利用来自世界各地母亲的现有纵向样本 妊娠与全面的生物库和严格的临床表型和2)收集纵向 从接受临床指示的疫苗的孕妇那里获得的样本是“增强”的(例如SARS-CoV-2、流感和 DPT)。这些新的焦点将促进首次系统分析纵向先天免疫和获得性免疫。 以及孕妇接种疫苗如何影响或扰乱孕妇的免疫健康。A续 临床核心的重点将是维护和扩大大量的孕妇血液和组织样本 并严格表型所有参与者，以解决临床变量的影响 与免疫紊乱(如体重指数、妊娠高血压疾病、糖尿病)有关。