Serological and functional impact of COVID-19 vaccination on the maternal fetal unit and infant immunity

项目摘要 随着COVID-19大流行继续伴随着新毒株的演变，我们承认已经奠定了基础 已经完成了对COVID-19疫苗接种或妊娠期疾病暴露后母体免疫力的评估，以及 抗体在脐带血和母乳中的被动传播。在这方面仍然存在着巨大的知识差距， 这一次涉及到第一，加强接种对妊娠期和哺乳期母体免疫力的影响， 考虑到新的应变，第二，了解被动的强度和耐久性， 通过母亲怀孕期间接种疫苗后婴儿血清学评价获得的婴儿免疫力，或 母乳喂养。鉴于最近开始的广泛的 向孕妇和哺乳期妇女接种新冠疫苗，现在又向她们接种加强剂， 毒性菌株COVID-19疫苗接种对母胎单位的影响需要通过分析来评估 妊娠期和产后对疫苗接种的母体血清学和免疫应答， 对母乳和脐带血进行评估，并进行婴儿血清学研究。我们提出了一个多臂队列 研究对COVID-19加强剂量、初始疫苗和 COVID-19疾病对母体胎儿单位和出生后婴儿免疫力的影响。这项免疫分析工作将 提供了母亲和婴儿体液介导免疫的有价值的特征， 妊娠期临床疫苗试验和方案，确定被动免疫对新生儿的潜在益处， 告知婴儿接种疫苗时间。COVID-19大流行促使免疫分析迅速启动 研究，但我们的研究是独一无二的：1）与迄今为止的研究不同，我们将评估纵向婴儿免疫力，以检查 从母体疫苗暴露中获得的功能性免疫2）我们正在建立一个现有的孕妇队列， 和哺乳期妇女暴露于COVID-19疾病和初始mRNA疫苗疗程，以及库存 对照样品，以便在评价疫苗/加强剂的免疫相关性时进行多重比较， 妊娠或哺乳期3）通过使用高度剂量节省、基于多重电致发光的测定， 表征SARS-CoV 2感染和疫苗接种的广泛抗体特征 COVID-1后母亲和新生儿血清学和功能性SARS CoV 2免疫谱的变化- 4）通过评估配对的母体、脐带血、母乳和婴儿血液， 将研究暴露时间和母体对长期新生儿和婴儿功能性免疫的作用; 5） 我们将使用机器学习来识别SARS-CoV 2免疫力的预测相关性， 疫苗研究，以最大限度地提高孕产妇和新生儿的免疫力。

PROJECT SUMMARY As COVID-19 pandemic continues with the evolution of new strains, we acknowledge the groundwork that has been done evaluating maternal immunity following COVID-19 vaccine or disease exposure in pregnancy, and passive transmission of antibodies in cord blood and breastmilk. There remains a significant knowledge gap at this time relating to first, the impact of booster vaccination on maternal immunity in pregnancy and lactation taking into consideration new strains, and second an understanding of the strength and durability of passively acquired infant immunity through evaluation of infant serology following maternal vaccination in pregnancy or breastfeeding. This knowledge gap has become even more significant in light of the recently started widespread administration of COVID vaccines and now booster doses to pregnant and breastfeeding women and new virulent strains. The impact of COVID-19 vaccination on the maternal-fetal unit needs to be assessed by profiling maternal serologic and immunologic response to vaccination during pregnancy and post partum, and expanding on assessment of breastmilk and cordblood with infant serological studies as well. We propose a multi arm cohort study to carry out a comprehensive evaluation of the impact of COVID-19 booster dose, initial vaccine, and COVID-19 disease on the maternal fetal unit and post-natal infant immunity. This immunoprofiling effort will provide a valuable characterization of humorally mediated immunity in both mother and infant that that can guide clinical vaccine trials and protocols in pregnancy, identify potential neonatal benefits from passive immunity, and inform timing of infant vaccination. The COVID-19 pandemic has prompted the rapid initiation of immunoprofiling studies, but ours is unique: 1) Unlike studies to date we will evaluate longitudinal infant immunity to examine the functional immunity gained from maternal vaccine exposures 2) We are building on an existing cohort of pregnant and lactating women exposed to COVID-19 disease and an initial mRNA vaccine course, as well as banked control samples, to allow for multiple comparison in evaluating immune correlates of vaccine/booster in pregnancy or lactation 3) by using highly dose-sparing, multiplex electroluminescence-based assays, it will characterize a wide range of antibody characteristics of SARS-CoV2 infection and vaccination to characterize the change in serological and functional SARS CoV2 immune profile in mother and neonate following COVID- 19 vaccine and booster exposure 4) by assessing paired maternal, cordblood, breastmilk, and infant blood we will study the role of timing of exposure and maternal on long term neonatal and infant functional immunity; 5) we will use machine-learning to identify predictive correlates of SARS-CoV2 immunity that could help guide vaccine research to maximize maternal and neonatal immunity.