Maternal Immunization and Determinants of Infant Immunity

母亲免疫和婴儿免疫缺陷综合征 （MADI） 传染病仍然是全世界5岁以下儿童死亡的主要原因。受影响最大的 是新生儿和一岁以内的婴儿。母亲和婴儿的免疫力是相互关联的。免疫 母亲的健康是孩子持续健康的关键。怀孕期间接种疫苗可提高产妇 免疫力，并具有提高新生儿对病原体的免疫力的巨大潜力。然而，主要差距 我们对怀孕的免疫学独特环境如何影响 免疫应答、母源性抗体转移规律以及母源性抗体与母源性抗体之间的相互作用 孕妇抗体和婴儿免疫系统。为了填补这一知识空白，我们提出了协同和 在三个目标下组织的多学科研究将： 1.区分怀孕期间疫苗诱导免疫的独特特征和预测因素。 2.界定母源抗体转移的原则。 3.确定婴儿免疫力和对疫苗反应的决定因素。 MADI由四个综合和协同的项目（P）和三个核心（C）组成：P1将决定影响力 妊娠对抗体生物物理和功能特征以及对疫苗的B/T细胞应答的影响。P2将识别 通过胎盘和母乳转移的内在因素。P3将识别转移的特征 母体Ab介导对病原体的免疫并调节婴儿的疫苗应答。P4将识别 母婴二分体中疫苗接种反应的细胞和分子预测因子。C1将提供切割- 边缘系统血清学和抗体工程技术，培训和质量控制。C2将提供集中式 管理和分析来自所有项目的数据，并将管理数据传播。管理核心将 提供管理和方案支助。 MADI团队结合了互补的专业知识，获得独特和良好的临床特征， 队列，和最先进的方法来剖析复杂的母婴免疫相互作用。 MADI在以下方面具有公共卫生意义和转化价值：1）调查孕产妇的免疫生物学 在新的广度和深度免疫; 2）确定新的可操作的目标，以提高有效性， 孕产妇免疫接种; 3）为疫苗设计和实施提供信息; 4）促进孕产妇免疫领域的发展。 婴儿免疫学和疫苗学通过产生新的分析工具，机械的见解，和丰富的假设- 生成系统免疫学数据集。这些知识可以改变孕产妇免疫领域。

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.