Defining the optimal type and timing of COVID-19 vaccine in pregnancy

项目摘要/摘要 怀孕的人更有可能需要有创机械通气或死于相关的并发症 到2019年冠状病毒病(新冠肺炎)比非孕妇。孕期接种新冠肺炎可以 预防母亲感染的后果，并通过以下途径为新生儿提供被动免疫 疫苗诱导的抗体胎盘转移。母体免疫系统经历适应性变化 以主动抑制对发育中的免疫反应为特征的 怀孕和促炎信号，以促进健康的植入和开始分娩。中环 假说是妊娠期间的获得性免疫变化导致发育的不同。 疫苗诱导的免疫取决于接种时的胎龄和/或所使用的疫苗平台。 这项提议的总体目标是解决重要的知识差距，包括有限的信息。 关于孕妇接种疫苗后的细胞免疫反应， 怀孕早期，以及不同疫苗平台之间的免疫原性比较。这项研究建议 是创新的，因为我们将使用一种全面的免疫图谱方法来量化功能细胞和 抗体反应，以确定新冠肺炎疫苗的类型和时机，以优化稳健和持久 母体疫苗诱导免疫(目标1)和新生儿胎盘病毒转移的被动免疫 中和抗体(目标2)。这项拟议的研究具有重要意义，因为它有望为 告知孕期接种新冠肺炎疫苗的临床建议，以改善孕产妇和新生儿 结果。长期目标将是为评估疫苗效力的更大规模研究提供初步数据 适用于孕妇及其新生儿。这项建议所提供的知识也将为未来 孕期其他重要和新出现病原体的疫苗开发。

PROJECT SUMMARY/ABSTRACT Pregnant individuals are more likely to require invasive mechanical ventilation or die from complications related to coronavirus disease 2019 (COVID-19) than non-pregnant women. COVID-19 vaccination in pregnancy can prevent the consequences of infection for the mother and provide passive immunity to newborns through placental transfer of vaccine-induced antibodies. The maternal immune system undergoes adaptive changes during pregnancy characterized by both active suppression of immune responses against the developing pregnancy and pro-inflammatory signals to promote healthy implantation and initiate labor. The central hypothesis is that the adaptive immunologic changes in pregnancy lead to differences in the development of vaccine-induced immunity depending on the gestational age at vaccination and/or the vaccine platform used. The overall objective of this proposal is to address important knowledge gaps including limited information regarding cellular immune responses following maternal vaccination, immune responses after vaccination in early pregnancy, and comparison of immunogenicity across different vaccine platforms. The research proposed is innovative because we will use a comprehensive immune profiling approach to quantify functional cellular and antibody responses in order to define the COVID-19 vaccine type and timing that optimizes robust and durable maternal vaccine-induced immunity (Aim 1) and neonatal passive immunity from placental transfer of viral neutralizing antibody (Aim 2). The proposed research is significant because it is expected to provide data to inform clinical recommendations for COVID-19 vaccines in pregnancy to improve maternal and neonatal outcomes. The long-term goal will be to provide preliminary data for a larger study evaluating vaccine efficacy for pregnant individuals and their neonates. The knowledge provided by this proposal will also inform future vaccine development for other important and emerging pathogens in pregnancy.