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

项目总结 随着新冠肺炎大流行继续伴随着新毒株的进化，我们承认已经 在孕期接种新冠肺炎或接触疾病后，已经完成了对母亲免疫力的评估，以及 脐带血和母乳中抗体的被动传播。仍然存在着巨大的知识差距， 这一次涉及第一，加强疫苗接种对孕期和哺乳期母亲免疫的影响 考虑到新的菌株，第二，理解被动的强度和耐久性 孕期或孕期接种疫苗后通过婴儿血清学评估获得婴儿免疫力 母乳喂养。鉴于最近开始的广泛传播，这种知识差距变得更加明显 接种COVID疫苗，现在增加了孕妇和哺乳期妇女以及新生的 毒力强的菌株。接种新冠肺炎疫苗对母婴单位的影响需要通过概况分析来评估 孕妇对孕期和产后接种疫苗的血清学和免疫学反应 婴儿血清学检查对母乳和脐带血检测的评价我们提出了一个多臂队列 研究开展对新冠肺炎加强免疫剂量、初始疫苗和 新冠肺炎病对母体胎儿单位和婴儿产后免疫的影响。这项免疫分析工作将 提供对母婴体液免疫的有价值的描述，这可以指导 怀孕期间的临床疫苗试验和方案，确定被动免疫对新生儿的潜在益处，以及 告知婴儿接种疫苗的时间。新冠肺炎大流行促使快速启动免疫图谱分析 研究，但我们的是独一无二的：1)与迄今的研究不同，我们将评估婴儿的纵向免疫能力，以检查 通过接触母体疫苗获得的功能免疫2)我们正在现有的孕妇队列的基础上 和接触新冠肺炎病的哺乳期妇女和最初的mrna疫苗疗程，以及银行 对照样本，以允许在评估疫苗/增强剂的免疫相关性时进行多重比较 怀孕或哺乳期3)通过使用高度节省剂量的多重电致发光检测，它将 SARS-CoV2感染的多种抗体特征及疫苗接种特征 COVID后母婴SARS CoV2血清学及免疫功能的变化 19)通过评估配对的孕妇、脐带血、母乳和婴儿的血液 将研究接触时间和母亲对新生儿和婴儿长期功能免疫的作用；5) 我们将使用机器学习来识别SARS-CoV2免疫的预测相关性，这可能有助于指导 疫苗研究，以最大限度地提高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.