Maternal Immunization and Determinants of Infant Immunity

总体摘要--母体免疫和婴儿免疫的决定因素 (马迪) 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 是一岁内的新生儿和婴儿。母婴免疫是相互关联的。免疫 母亲的健康是孩子持续健康的关键。孕期接种疫苗可提高产妇的孕期 免疫能力强，在提高新生儿对病原体的免疫力方面具有巨大潜力。然而，主要差距是 保持我们对独特的妊娠免疫环境如何影响的理解 免疫应答、母源抗体传递规律及传递之间的相互作用 母体抗体与婴儿免疫系统。为了填补这一知识空白，我们提出了协同和 按三个目标组织的多学科研究将： 1.识别孕期疫苗诱导免疫的独特特征和预测因素。 2.界定母体抗体转移的原则。 3.确定婴儿免疫的决定因素和对疫苗的反应。 MADI由四个综合和协同项目(P)和三个核心(C)组成：P1将决定影响 妊娠对抗体生物物理和功能特征以及B/T细胞对疫苗反应的影响。P2将确定 AB-通过胎盘和母乳转移的内在因素。P3将识别被转移的特征 母源抗体介导对病原体的免疫和调节婴儿的疫苗反应。P4将确定 母婴对接种疫苗反应的细胞和分子预测因子。C1将提供切割- EDGE系统血清学和抗体工程技术、培训和质量控制。C2将提供集中的 管理和分析所有项目的数据，并将管理数据传播。管理核心将 提供管理和方案支持。 MADI团队结合了互补的专业知识，获得独特和有特色的临床 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1)研究母体免疫生物学方面具有公共卫生意义和翻译价值 在新的广度和深度进行免疫；2)确定新的可操作目标，以提高预防接种的有效性 母体免疫；3)为疫苗设计和实施提供信息；4)刺激母体免疫领域- 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.