Research Project 2 The pregnancy AdaptOME

项目2：摘要 虽然传统上被认为是一种普遍的致耐受性状态，但新的数据表明， 远非简单的抗炎转变，而是以从炎症到耐受的戏剧性转变为特征 以适应胎儿的变化。这些免疫系统的巨大变化 反应是在精密的时间控制下，并伴随着显着的变化，在离体 细胞反应然而，这些免疫动力学如何控制全身免疫反应， 仍然不完全理解。越来越多的数据表明怀孕期间的免疫脆弱性， 增强了对呼吸道病毒感染的易感性，包括流感和SARS-CoV-2， 疫苗诱导免疫。然而，妊娠期免疫反应的演变如何影响整体 对疫苗接种的反应，它如何影响抗体转移到婴儿的质量，以及这些变化 可能会影响出生后保护的持久性仍然不完全清楚。然而，我们正处于一个独特的 这是历史上的一个时刻，许多新的疫苗平台正在向孕妇推出， 抗击SARS-CoV-2。除了目前EUA批准的疫苗外，还将出现其他疫苗， 能够比较mRNA、腺病毒载体和含佐剂的蛋白质平台比较，所有这些都 将在整个怀孕期间被推荐，以提高大多数未经治疗的孕妇及其婴儿的免疫力。 然而，疫苗增强先前感染的母亲的免疫力以及增强 未来，在先前免疫的母亲中使用异源初免/加强策略将提供独特的 有机会开始确定能够在妊娠期最大限度地提高免疫力的疫苗策略。此外，委员会认为， 与推荐的流感和百日咳加强疫苗有关，该财团将有一个难得的机会， 对比召回/从头、同源/异源和不同疫苗诱导的免疫应答 在怀孕的4个三个月的平台，提供了一个机会，以产生基础数据， T和B细胞免疫的免疫编程。使用专有和已建立的系统免疫学 分析工具，该联盟将重点放在项目2的绘图广泛的抗体OME和疫苗诱导 体液免疫应答以及分析SARS-CoV-2、流感和百日咳特异性B和T 细胞转录组这些数据将构成第一个怀孕疫苗的基础，指导下一代 疫苗和治疗设计，以选择性地利用和最大限度地保护整个母体：胎儿二分体。

Project 2: Summary While traditionally regarded as a generalized tolerogenic state, emerging data suggest that pregnancy is far from a simple anti-inflammatory shift but is characterized by dramatic shifts from inflammation to tolerance over the course of pregnancy, to accommodate changes in the fetus. These dramatic shifts in the immune response are under exquisite chronological control and are accompanied by significant changes in ex vivo cellular responsiveness. However, how these immunological dynamics control the systemic immune response remains incompletely understood. Accumulating data point to immune vulnerabilities during pregnancy, with enhanced susceptibility to respiratory viral infectious including influenza and SARS-CoV-2 as well as dampened vaccine induced immunity. However, how the evolving immune response over gestation affects the overall response to vaccination, how it influences the quality of antibody transfer to infant, as well as how these changes may influence durability of protection after birth remains incompletely understood. Yet, we are at a unique moment in history, where a number of novel vaccine platforms are being rolled out to pregnant women in the battle against SARS-CoV-2. In addition to the currently EUA approved vaccines, additional vaccines will emerge, enabling the comparison of mRNA, adenoviral vectors, and adjuvanted protein platform comparisons, all of which will be recommended throughout pregnancy to drive immunity in largely naïve pregnant women and their infants. However, the ability of vaccines to boost immunity in previous infected mothers as well as to boost immunity in the future in previously immunized mothers using heterologous prime/boosting strategies will provide a unique opportunity to begin to define the vaccine strategies able to maximally drive immunity over gestation. Moreover, linked to recommended booster vaccines to Influenza and Pertussis, this consortium will have a rare opportunity to contrast immune responses induced by recall/de novo, homologous/heterologous, and distinct vaccine platforms across the 4 trimesters of pregnancy, providing an opportunity to generate the foundational data on immune programming of T and B cell immunity. Using both proprietary and established systems immunology profiling tools, the consortium will focus in Project 2 on mapping the broad antibody-OME and vaccine induced humoral immune responses as well as to profile the SARS-CoV-2-, Influenza- and Pertussis-specific B and T cell transcriptome. These data will form the basis of the first pregnant Vaccine-OME to guide next generation vaccine and therapeutic design to selectively leverage and maximize protection across the maternal:fetal dyad.