Maternal Immunization and Determinants of Infant Immunity

母亲免疫接种和婴儿免疫的决定因素

• 批准号: 10203485
• 负责人: Marcela F Pasetti
• 金额: $ 318.86万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-12 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10203485
• 关键词: 5 year old; Address; Adult; Affect; Animal Model; Antibodies; Antibody-mediated protection; Biophysics; Cause of Death; Cells; Child; Childhood; Clinical; Communicable Diseases; Complex; Data Analyses; Data Science; Data Set; Development; Effectiveness; Environment; Goals; Health; Human Milk; Immune; Immune response; Immune system; Immunity; Immunization; Immunobiology; Immunologics; Immunology; Immunotherapy; In Vitro; Infant; Infant Health; Infection; Infectious Agent; Infectious Disease Immunology; Influenza; Intervention; Intrinsic factor; Knowledge; Learning; Life; Link; Logistics; Maternal Health; Maternal and Child Health; Maternal antibody; Maternally-Acquired Immunity; Mediating; Methods; Molecular; Monoclonal Antibodies; Morbidity - disease rate; Mothers; Newborn Infant; Pathway interactions; Pertussis; Placenta; Predisposition; Pregnancy; Pregnant Women; Productivity; Public Health; Quality Control; Research; Research Personnel; Role; Series; Serology; Specimen; Structure; System; T cell response; Technology; Tetanus; Time; Tissue Model; Training; Vaccination; Vaccine Design; Vaccines; analytical tool; antibody engineering; antibody transfer; cohort; data dissemination; data management; fitness; human tissue; improved; infection burden; insight; interest; longitudinal analysis; low and middle-income countries; maternal vaccination; mortality; multidisciplinary; multimodality; neonatal immunity; novel; pathogen; predicting response; prevent; programs; response; success; translational research program; vaccine response; vaccine-induced antibodies; vaccine-induced immunity; vaccinology

OVERALL ABSTRACT – MATERNAL IMMUNIZATION AND DETERMINANTS OF INFANT IMMUNITY (MADI) Infectious diseases remain the leading cause of death in children under 5 years worldwide. The most affected are newborns and infants within the first year of life. Maternal and infant immunity are interrelated. Immune fitness of the mother is key to sustained health of a child. Vaccination during pregnancy enhances maternal immunity and has a tremendous potential to improve neonatal immunity to pathogens. However, major gaps remain in our understanding of how the immunologically unique setting of pregnancy influences responses to vaccination, the rules of maternal Ab transfer, and the interactions between transferred maternal Ab and the infant immune system. To fill this knowledge gap, we have proposed synergistic and multidisciplinary studies organized in three Aims that will: 1. Distinguish unique features and predictors of vaccine-induced immunity during pregnancy. 2. Define the principles governing maternal antibody transfer. 3. Identify determinants of infant immunity and responses to vaccines. MADI consists of four integrated and synergistic Projects (P) and three Cores (C): P1 will determine the influence of pregnancy on Ab biophysical and functional features and on B/T cell responses to vaccines. P2 will identify Ab-intrinsic factors underlying transfer via placenta and breast milk. P3 will identify features of transferred maternal Ab mediating immunity to pathogens and regulating vaccine responses in infants. P4 will identify cellular and molecular predictors of responses to vaccination in the mother-infant dyad. C1 will provide cutting- edge systems serology and Ab engineering technologies, training, and quality control. C2 will provide centralized management and analysis of data from all projects and will manage data dissemination. The Admin Core will provide management and programmatic support. The MADI team combines complementary expertise, access to unique and well characterized clinical cohorts, and state-of-the-art methods to dissect complex maternal-infant immune interactions. MADI has public health significance and translational value in 1) investigating the immunobiology of maternal immunization at a new breadth and depth; 2) identifying novel actionable targets to improve effectiveness of maternal immunization; 3) informing vaccine design and implementation; and 4) stimulating the field of maternal- infant immunology and vaccinology by generating new analytical tools, mechanistic insights, and rich hypothesis- generating systems immunology datasets. Such knowledge can transform the field of maternal immunization.

总体摘要 - 婴儿免疫的产妇免疫和决定因素 （Madi） 在全球5岁以下儿童中，传染病仍然是死亡的主要原因。受影响最大的 是新生儿和婴儿生命的第一年。母亲和婴儿免疫相互关联。免疫 母亲的适应性是孩子持续健康的关键。怀孕期间的疫苗接种可增强母猪 免疫力，并且具有改善新生儿免疫力的巨大潜力。但是，主要差距 保持我们对免疫学上独特怀孕的影响如何影响的理解 对疫苗接种的反应，母体AB转移的规则以及转移之间的相互作用 孕产妇AB和婴儿免疫系统。为了填补这一知识差距，我们提出了协同作用和 多学科研究以三个目标组织： 1。区分怀孕期间疫苗诱导的免疫力的独特特征和预测指标。 2。定义管理抗体转移的原理。 3。确定婴儿免疫和对疫苗的反应。 MADI由四个集成和协同项目（P）和三个核心（C）组成：P1将决定影响的影响 AB生物物理和功能特征以及B/T细胞对疫苗的反应的怀孕。 P2将识别 通过plapica和母乳转移的基础因素。 P3将确定转移的功能 母体AB介导对病原体的免疫力并调节婴儿的疫苗反应。 P4将识别 母节对母亲疫苗接种反应的细胞和分子预测指标。 C1将提供剪裁 - 边缘系统血清学和AB工程技术，培训和质量控制。 C2将提供集中式 所有项目的数据管理和分析，并将管理数据传播。管理员核心将 提供管理和程序化支持。 MADI团队结合了完善的专业知识，获得独特且特征良好的临床 剖析复杂的产妇免疫相互作用的同类和最先进的方法。 MADI在1）研究产妇的免疫生物学中具有公共卫生的意义和翻译价值 在新的宽度和深度上进行免疫接种； 2）确定新颖的可行目标以提高 孕产妇免疫； 3）通知疫苗设计和实施； 4）刺激母体的领域 通过产生新的分析工具，机械见解和丰富的假设 - 生成系统免疫学数据集。这种知识可以改变母体免疫抑制的领域。