Infant Immunity

项目3--摘要 从母亲转移到胎儿的抗体是最初几个月免疫的核心决定因素 生活的一部分。当婴儿抗体的大小和亲和力增加时，它们可提供对感染病原体的保护 反响相对较低。另一方面，母体抗体会降低婴儿的疫苗反应， 这种现象被称为疫苗干扰。抗病毒抗体依赖免疫的机制 对早期生命中的病原体和疫苗反应的调节仍然知之甚少。这种知识上的鸿沟 限制了为幼儿提供最佳保护的产妇免疫战略的基本原理设计。这个 该项目的总体目标是确定关键的生物物理(亚类和糖基化特征)和功能特征 (天然免疫效应器的激活)传递的母体抗体介导病原体控制和 调节婴幼儿的疫苗反应。该项目的重点是选定的两种模式病原体 整个计划，百日咳和流感。将使用系统血清学方法来表征 孕期免疫后母体抗体转移给新生儿的功能特性 以及母体免疫对婴儿疫苗反应质量的影响。人的工程学 抗体和对基因缺陷和人源化小鼠的过继转移将被用来确定这种作用 转移的母源抗体的特定生物物理特征及其与婴儿免疫球蛋白Fc的相互作用 受体和补体在控制病原体和调节疫苗反应中的作用。协同增效 对于项目1和项目2，项目3将提供对监管的功能影响的机械性洞察 妊娠引起的疫苗反应，母体抗体通过胎盘的选择性转移及其 出生后腐烂，在婴儿期对病原体具有免疫力。与项目4协同，项目3将定义 转移的母体抗体与婴儿免疫系统相互作用的功能意义 用于婴儿期的疫苗反应。通过该项目获得的知识将提供前所未有的洞察力 在母婴免疫的免疫生物学方面，并将为疫苗的发展和 在生命早期对传染病提供最佳保护的单抗。

PROJECT 3 – ABSTRACT Antibodies transferred from the mother to the fetus are a central determinant of immunity during the first months of life. They provide protection against infectious pathogens when the magnitude and avidity of infant antibody responses are relatively low. On the other hand, maternal antibodies can decrease infant vaccine responses, a phenomenon named vaccine interference. The mechanisms underlying antibody-dependent immunity against pathogens and regulation of vaccine responses in early life remain poorly understood. This gap in knowledge limits the rationale design of maternal immunization strategies providing optimal protection to young infants. The overall aim of the project is to identify key biophysical (subclass and glycosylation profile) and functional features (activation of innate immune effectors) of transferred maternal antibodies mediating pathogen control and regulating vaccine responses in young infants. The project is focused on the two model pathogens selected for the whole program, pertussis and influenza. A systems serology approach will be used to characterize the functional properties of maternal antibodies transferred to the newborn following immunization during pregnancy and the impact of maternal immunization on the quality of infant vaccine responses. Engineering of human antibodies and adoptive transfer to genetically deficient and humanized mice will be used to determine the role of specific biophysical features of transferred maternal antibodies and of their interactions with infant IgG Fc receptors and complement in the control of pathogens and in the regulation of vaccine responses. Synergizing with Projects 1 and 2, Project 3 will provide mechanistic insight in the functional implications of the regulation of vaccine responses by pregnancy, the selective transfer of maternal antibodies across the placenta and their decay after birth for immunity to pathogens in infancy. Synergizing with project 4, project 3 will define the functional implications of the interactions between transferred maternal antibodies and the infant immune system for vaccine responses in infancy. The knowledge gained through the project will provide unprecedented insight in the immunobiology of maternal and infant immunization and will inform the development of vaccines and monoclonal antibodies providing optimal protection against infectious diseases in early life.