Research Project 2 The pregnancy AdaptOME

研究项目 2 怀孕 AdaptOME

• 批准号: 10420110
• 负责人: Boris Dominik Juelg
• 金额: $ 47.08万
• 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/10420110
• 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; Clone Cells; Communicable Diseases; Data; Data Analyses; Disease; Emergency Situation; Fetal Growth; Fetus; Foundations; Future; Genetic; Health Personnel; Human Milk; Immune; Immune response; Immunity; Immunization; Immunize; Immunologics; Immunology; Infant; Infection; Inflammation; Inflammatory; Influenza; Influenza A Virus, H1N1 Subtype; Link; 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; 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：摘要 虽然传统上被认为是广泛的耐受性状态，但新兴数据表明怀孕是 远非简单的抗炎转移，但其特征是从炎症到公差的急剧转移 在整个怀孕过程中，以适应胎儿的变化。这些免疫中的戏剧性转移 响应是在按时间顺序控制的，伴随着体内的重大变化 细胞响应能力。但是，这些免疫动力如何控制全身免疫反应 仍然不完全理解。累积数据指向怀孕期间免疫脆弱性的指示 增强了对呼吸道病毒感染的易感性，包括影响力和SARS-COV-2以及该死的 疫苗诱导免疫力。但是，妊娠的免疫反应如何影响整体 对疫苗的反应，它如何影响抗体转移到婴儿的质量，以及它们如何改变 可能会影响出生后的保护耐用性，但仍未完全理解。但是，我们处于独特之处 历史上的时刻，许多新型疫苗平台正在向孕妇推出 与SARS-COV-2战斗。除了当前批准的疫苗外，还将出现其他疫苗， 可以比较mRNA，腺病毒载体和调整的蛋白质平台比较 建议在整个怀孕期间推荐在很大程度上幼稚的孕妇及其婴儿的免疫力。 但是，疫苗在以前受感染的母亲中提高免疫史的能力以及在 以前免疫母亲使用异源/增强策略的未来将提供独特的 开始定义疫苗策略的机会，可以最大程度地推动免疫接种。而且， 该财团与推荐给流感和百日咳的促进疫苗有关，将有一个难得的机会 对比召回/de从头，同源/异源和独特的疫苗引起的免疫反应 怀孕四个三个孕妇的平台，提供了一个机会，以生成有关的基础数据 T和B细胞免疫学的免疫编程。使用专有和已建立的系统免疫学 该财团分析工具，将重点放在项目2上 体液免疫反应以及介绍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种指导下一代的怀孕疫苗的基础 疫苗和热设计可有选择地利用和最大化整个母校的保护：胎儿二元。