Research Project 2 The pregnancy AdaptOME

研究项目 2 怀孕 AdaptOME

• 批准号: 10611530
• 负责人: Boris Dominik Juelg
• 金额: $ 79.67万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-19 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10611530
• 关键词: 2019-nCoV; Adenovirus Vector; Adjuvant; Affect; Allografting; Anti-Inflammatory Agents; Antibodies; Antibody titer measurement; Antigens; Atlases; Awareness; B-Lymphocytes; Biochemical; Birth; COVID-19 pandemic; COVID-19 vaccine; Case Fatality Rates; Cellular Assay; Cessation of life; Chronology; Clinical; Communicable Diseases; Data; Data Analyses; Disease; Eligibility Determination; Emergency Situation; Fetal Growth; Fetus; Future; Genetic; Growth; Health Personnel; Human Milk; Immune; Immune response; Immunity; Immunization; Immunize; Immunologics; Immunology; Infant; Infection; Inflammation; Inflammatory; Influenza; Influenza A Virus, H1N1 Subtype; Link; Maps; Maternal-fetal medicine; Messenger RNA; Morbidity - disease rate; Mothers; Newborn Infant; Pertussis; Phase; Phenotype; Placentation; Population; Predisposition; Pregnancy; Pregnancy Trimesters; Pregnant Women; Property; Proteins; RNA vaccine; Race; Recommendation; Recording of previous events; Research Project Grants; Safety; Sampling; Serology; Shapes; Specialist; Syndrome; System; T cell response; T-Lymphocyte; Therapeutic; Vaccination; Vaccine Design; Vaccines; Viral; Vulnerable Populations; Woman; Work; adaptive immune response; antibody transfer; booster vaccine; comorbidity; coronavirus disease; design; experience; fetal; hemodynamics; immune function; immune reconstitution; immunogenic; implantation; infection risk; mortality; neonate; next generation; novel; novel vaccines; pandemic disease; phase III trial; pregnant; rational design; respiratory; response; success; therapy design; tool; transcriptome; vaccine distribution; vaccine platform; vaccine response; vaccine safety; vaccine strategy; vaccine-induced antibodies; vaccine-induced immunity

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.

项目2：总结 虽然传统上被认为是一种普遍的耐受状态，但新出现的数据表明，怀孕是 远不是简单的抗炎转变，而是以从炎症到耐受的戏剧性转变为特征 在怀孕期间，以适应胎儿的变化。免疫系统的这些戏剧性变化 反应在精确的时间顺序控制下，并伴随着体外显著的变化 手机响应性。然而，这些免疫动力学如何控制全身免疫反应 仍然没有完全被理解。越来越多的数据表明怀孕期间存在免疫漏洞， 增加对包括流感和SARS-CoV-2在内的呼吸道病毒感染的易感性，并抑制 疫苗可诱导免疫。然而，妊娠期间不断演变的免疫反应如何影响整体 对接种疫苗的反应，它如何影响向婴儿传递抗体的质量，以及这些变化是如何发生的 可能会影响出生后保护的持久性仍不完全清楚。然而，我们正处于一个独特的 历史时刻，一些新的疫苗平台正在向世界各地的孕妇推出 抗击SARS-CoV-2的战斗。除了目前欧盟批准的疫苗外，还将出现更多疫苗， 实现了对mRNA、腺病毒载体和佐剂蛋白平台的比较，所有这些 将在整个怀孕期间被推荐，以提高大部分天真孕妇及其婴儿的免疫力。 然而，疫苗能够提高以前感染过的母亲的免疫力，以及提高 未来在以前接种过疫苗的母亲中使用异种激发/增强策略将提供一种独特的 有机会开始确定能够最大限度地提高妊娠期免疫力的疫苗策略。此外， 将推荐的流感和百日咳加强疫苗联系起来，这个联盟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 平台跨越怀孕的4个三个月，提供了一个机会来生成关于 T细胞和B细胞免疫的免疫程序。使用专有的和已建立的系统免疫学 分析工具，该联盟将在项目2中专注于绘制广泛的抗体-OME和疫苗诱导的 体液免疫反应以及SARS-CoV-2、流感和百日咳特异性B和T的分析 细胞转录组。这些数据将形成第一个怀孕疫苗的基础-OME，以指导下一代 疫苗和治疗设计，选择性地利用和最大限度地保护母体：胎儿二元体。