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 U19的总体目标是阐明妊娠免疫组，因为它控制着母亲和胎儿的健康。一 在怀孕过程中，对先天性和适应性免疫反应的认识存在很大差距 以及在怀孕的每三个月，免疫信号的扰动如何表现在可归因于 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- 同种异体胎儿，同时保护自己和胎儿免受病原体的挑战。全面揭示 通过妊娠期母体免疫功能的研究，无疑将使我们对母体免疫功能有更深入的了解。 流感和COVID-19等疾病的发病率和死亡率，因此， 无法识别的治疗窗口。目前预防孕产妇发病的疗法包括接种疫苗， 对母亲和胎儿都有好处。然而，我们的能力，最大限度地提高孕产妇和胎儿的利益， 由于对母体免疫力不断变化的性质的认识存在很大差距， 整个妊娠期。母亲接种疫苗，如流感疫苗，可增强免疫力， 季节性流感造成的孕产妇发病率和死亡率。母亲普遍接种流感疫苗 建议产妇受益。母亲接种流感疫苗对胎儿的益处是一个值得注意的额外因素， 疫苗接种对孕妇有好处，但不是孕妇接种疫苗的主要推动力。相反，母性 疫苗接种可用于在对胎儿没有已知益处的情况下对胎儿具有直接益处。 母亲（例如DPT）。虽然母亲接种疫苗用于母亲和胎儿两者的益处，但缺乏免疫接种是不可能的。 有关怀孕期间免疫力的知识，以及它如何随着胎龄和外部刺激（例如 病毒感染、疫苗接种），极大地阻碍了母亲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支持本提案中的所有项目， 获得一个新的种族和族裔多样化的怀孕队列。这些独特的群体将支持我们的 母亲组学最大化免疫力（MOMi）核心将有两个焦点， 存在巨大的知识差距：1）利用来自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 来自接受临床指示疫苗作为"加强"（例如SARS-CoV-2、Flu和 DPT）。这些新的焦点将有助于首次系统分析纵向先天性和适应性免疫， 怀孕的个体以及母亲接种疫苗如何影响或干扰怀孕的免疫健康。继续 临床核心的重点将是维持和扩大一个大型的血液和组织样本库， 个体，并严格表型所有参与者，以解决临床变量的影响 与免疫紊乱相关（例如BMI、妊娠期高血压疾病、糖尿病）。