Infant Immunity

项目3 -摘要 从母体转移到胎儿体内的抗体是最初几个月免疫力的主要决定因素 生命当婴儿抗体的数量和亲和力降低时， 反应相对较低。另一方面，母体抗体可降低婴儿疫苗应答， 这种现象被称为疫苗干扰。抗体依赖性免疫的机制 对生命早期的病原体和疫苗应答的调节仍然知之甚少。这种知识上的差距 限制了为幼儿提供最佳保护的孕产妇免疫战略的合理设计。的 该项目的总体目标是确定关键的生物物理（亚类和糖基化谱）和功能特征 转移的母体抗体介导病原体控制和 调节幼儿的疫苗反应。该项目的重点是两个模式病原体选择， 整个项目，百日咳和流感系统血清学方法将用于表征 妊娠期免疫后母源抗体转移至新生儿的功能特性 以及母亲免疫接种对婴儿疫苗应答质量的影响。人体工程学 抗体和过继转移到遗传缺陷和人源化小鼠将被用来确定的作用 转移的母体抗体的特定生物物理特征及其与婴儿IgG Fc抗体的相互作用 受体和补体在控制病原体和调节疫苗应答中的作用。协同作用 与项目1和2，项目3将提供机械的洞察力的功能影响的监管， 妊娠的疫苗反应，母体抗体通过胎盘的选择性转移及其 婴儿期对病原体的免疫力。与项目4协同，项目3将确定 转移的母体抗体与婴儿免疫系统之间相互作用的功能意义 for vaccine疫苗responses应答in infant婴儿.通过该项目获得的知识将提供前所未有的洞察力 在孕产妇和婴儿免疫的免疫生物学，并将告知疫苗的发展， 单克隆抗体提供最佳的保护，防止感染性疾病在生命早期。

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.