Induction and maintenance of SARS-CoV-2 mRNA vaccine-specific memory across tissues

跨组织的 SARS-CoV-2 mRNA 疫苗特异性记忆的诱导和维持

• 批准号: 10751246
• 负责人: Julia Meghan Davis-Porada
• 金额: $ 4.92万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10751246
• 关键词: 2019-nCoV; Adult; Affect; Age; Antibody Formation; Antibody titer measurement; Attenuated; Authorization documentation; B-Lymphocytes; Blood; Blood specimen; COVID-19 pandemic; COVID-19 vaccine; Cell physiology; Cells; Child; Clinical; Collaborations; Communities; Data; Development; Enzyme-Linked Immunosorbent Assay; Event; Exhibits; Flow Cytometry; Frequencies; Future; Goals; Health; Human; Humoral Immunities; Immune; Immune response; Immune system; Immunity; Immunologic Memory; Individual; Infection; Inflammatory; Integration Host Factors; Interferons; Investigation; Knowledge; Laboratories; Life; Lung; Lymphocyte; Lymphoid; Lymphoid Tissue; Macrophage; Maintenance; Measures; Mediating; Medical; Memory; Memory B-Lymphocyte; Modeling; Moderna COVID-19 vaccine; Monitor; Mononuclear; Morbidity - disease rate; Mucous Membrane; Natural Immunity; Organ Donor; Organ Procurements; Outcome; Persons; Phenotype; Population; Prevention strategy; Production; Property; Proteins; RNA vaccine; Residencies; Resources; Role; Serology; Site; Spatial Distribution; T memory cell; T-Lymphocyte; Time; Tissue Donors; Tissues; Vaccinated; Vaccination; Vaccine Design; Vaccinee; Vaccines; Variant; Viral; Virus; Virus Diseases; Work; adaptive immunity; authority; coronavirus disease; current pandemic; cytokine; frontier; high dimensionality; human tissue; improved; lymph nodes; lymphoid organ; manufacture; mortality; neutralizing antibody; novel; novel vaccines; pandemic disease; pathogen; prevent; quantitative imaging; respiratory virus; response; severe COVID-19; tissue resource; unvaccinated; vaccine development; vaccine distribution; vaccine efficacy; vaccine formulation; vaccine response; vaccine strategy; vaccine trial; vaccine-induced immunity; vaccinology; 2019-nCoV; Adult; Affect; Age; Antibody Formation; Antibody titer measurement; Attenuated; Authorization documentation; B-Lymphocytes; Blood; Blood specimen; COVID-19 pandemic; COVID-19 vaccine; Cell physiology; Cells; Child; Clinical; Collaborations; Communities; Data; Development; Enzyme-Linked Immunosorbent Assay; Event; Exhibits; Flow Cytometry; Frequencies; Future; Goals; Health; Human; Humoral Immunities; Immune; Immune response; Immune system; Immunity; Immunologic Memory; Individual; Infection; Inflammatory; Integration Host Factors; Interferons; Investigation; Knowledge; Laboratories; Life; Lung; Lymphocyte; Lymphoid; Lymphoid Tissue; Macrophage; Maintenance; Measures; Mediating; Medical; Memory; Memory B-Lymphocyte; Modeling; Moderna COVID-19 vaccine; Monitor; Mononuclear; Morbidity - disease rate; Mucous Membrane; Natural Immunity; Organ Donor; Organ Procurements; Outcome; Persons; Phenotype; Population; Prevention strategy; Production; Property; Proteins; RNA vaccine; Residencies; Resources; Role; Serology; Site; Spatial Distribution; T memory cell; T-Lymphocyte; Time; Tissue Donors; Tissues; Vaccinated; Vaccination; Vaccine Design; Vaccinee; Vaccines; Variant; Viral; Virus; Virus Diseases; Work; adaptive immunity; authority; coronavirus disease; current pandemic; cytokine; frontier; high dimensionality; human tissue; improved; lymph nodes; lymphoid organ; manufacture; mortality; neutralizing antibody; novel; novel vaccines; pandemic disease; pathogen; prevent; quantitative imaging; respiratory virus; response; severe COVID-19; tissue resource; unvaccinated; vaccine development; vaccine distribution; vaccine efficacy; vaccine formulation; vaccine response; vaccine strategy; vaccine trial; vaccine-induced immunity; vaccinology

PROJECT SUMMARY Vaccines save lives, and the rapid development of novel vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was a triumph for the medical community. While the rapid deployment of these vaccines has undoubtedly attenuated the severe morbidity and mortality induced by the virus, their efficacy is decreased against variant strains, in children, and with increasing time post-administration. These clinical findings highlight our lack of understanding of how durable, protective immunity is induced by vaccination and how this varies across the population. Studying vaccine induced memory in humans has two major challenges. First, viral exposures over life confound the identification of vaccine-specific memory; second, the stores of memory lymphocytes reside in the tissues, which makes monitoring the vaccine response in healthy individuals challenging. The SARS-CoV-2 pandemic affords us the unique opportunity to study the response to a novel vaccine formulation without confounding natural antigenic exposure and the ability to distinguish infection from vaccination by serology. Additionally, our unique organ donor tissue resource provides a validated model to investigate tissue-localized vaccine-specific immunity. The goal of this proposal is to understand how vaccine- induced immune memory is distributed across tissue and affected by host factors such as age. The central hypothesis of this proposal is that induction and maintenance of vaccine-specific memory is controlled in lymph nodes, and specific early induction events directly impact immune memory development and vary with age. I will address this hypothesis and meet the goals of the study by using flow cytometry and high- dimensional sequencing to evaluate the relationship between circulating and tissue-localized vaccine memory and how they differ in phenotype, function, and across age. I will also investigate how the initial, inflammatory host-specific response to the mRNA-1273 vaccine differs across age and correlates to the quantity of immune memory induced. The results of this study will elucidate the importance of lymph nodes in the vaccine response and highlight the benefits and downfalls of mRNA vaccines across various host factors. These results will have implications for future vaccine design and may play a role in managing both the SARS-CoV-2 pandemic and any future ones.

项目摘要 疫苗可以挽救生命，以及针对严重急性呼吸系统综合征的新型疫苗的快速开发 冠状病毒2（SARS-COV-2）是医学界的胜利。而这些迅速部署 疫苗无疑已衰减病毒引起的严重发病率和死亡率，其功效是 对变异菌株，儿童和管理后时间的增加减少。这些临床 调查结果突显了我们对疫苗接种和 这在整个人群中如何变化。研究疫苗诱导的人类记忆有两个主要挑战。 首先，病毒暴露在生命中混淆了疫苗特异性记忆的识别；第二，商店 记忆淋巴细胞位于组织中，这使得监测健康个体的疫苗反应 具有挑战性的。 SARS-COV-2大流行为我们提供了研究小说的反应的独特机会 疫苗配方而不混淆天然抗原暴露，并且能够区分感染与 血清学疫苗接种。此外，我们独特的器官捐赠组织资源为 研究组织中定位的疫苗特异性免疫。该提案的目的是了解疫苗如何 诱导的免疫记忆分布在组织之间，并受宿主因素（例如年龄）的影响。中央 该提议的假设是，在控制疫苗特定记忆的诱导和维护中 淋巴结和特定的早期诱导事件直接影响免疫记忆发展和 随着年龄的增长而变化。我将通过使用流式细胞术和高 - 尺寸测序以评估循环和组织局部疫苗记忆之间的关系 以及它们在表型，功能和跨年龄上的不同。我还将研究最初的炎症 对mRNA-1273疫苗的宿主特异性反应在年龄之间有所不同，并与免疫的量相关 记忆引起。这项研究的结果将阐明淋巴结在疫苗中的重要性 反应并突出了各种宿主因素中mRNA疫苗的益处和下降。这些 结果将对未来的疫苗设计产生影响，并可能在管理SARS-COV-2中发挥作用 大流行和任何未来的人。