Research Project 2 The pregnancy AdaptOME

研究项目 2 怀孕 AdaptOME

基本信息

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
项目类别：
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

项目摘要

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，怀孕是远非简单的抗炎转变，而是从炎症到耐受的巨大转变在怀孕过程中，以适应胎儿免疫系统的这些巨大变化。反应受到精确的时间顺序控制，并伴随着离体的显着变化然而，这些免疫动力学如何控制全身免疫反应。积累的数据表明怀孕期间的免疫脆弱性仍然不完全清楚。对呼吸道病毒感染（包括流感和 SARS-CoV-2）的易感性增强，并受到抑制然而，妊娠期间不断变化的免疫反应如何影响整体。对疫苗接种的反应，它如何影响抗体转移给婴儿的质量，以及这些变化如何可能会影响出生后保护的持久性仍不完全清楚，但我们正处于一个独特的时期。历史性的时刻，许多新型疫苗平台正在向孕妇推出除了目前 EUA 批准的疫苗外，还会出现其他疫苗，能够比较 mRNA、腺病毒载体和佐剂蛋白平台比较，所有这些将建议在整个怀孕期间使用，以提高大部分未接触过的孕妇及其婴儿的免疫力。然而，疫苗可以增强既往感染过的母亲的免疫力，也可以增强已感染母亲的免疫力。未来，使用异源初免/加强策略的先前免疫母亲将提供独特的有机会开始确定能够最大限度地提高妊娠期间免疫力的疫苗策略。与推荐的流感和百日咳加强疫苗相关，该联盟将获得难得的机会对比由召回/从头、同源/异源和不同疫苗诱导的免疫反应跨越怀孕四个月的平台，提供了生成基础数据的机会使用专有和成熟的系统免疫学对 T 和 B 细胞免疫进行免疫编程。分析工具，该联盟将在项目 2 中重点关注绘制广泛的抗体 OME 和疫苗诱导的图谱体液免疫反应以及分析 SARS-CoV-2、流感和百日咳特异性 B 型和 T 型这些数据将构成第一个怀孕疫苗-OME的基础，以指导下一代。疫苗和治疗设计有选择地利用和最大限度地保护母体：胎儿二人组。