Molecular tracking of antigen following vaccination

疫苗接种后抗原的分子追踪

基本信息

批准号：
10307136
负责人：
Beth Ann Tamburini
金额：
$ 18.88万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-11-23 至 2023-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10307136
关键词：
Accounting Address Adjuvant Antigen Presentation Antigens Archives Attenuated Attenuated Vaccines CD8-Positive T-Lymphocytes Cell Communication Cell Death Cells Cellular Immunity DNA Data Dendritic Cells Devices Gene Expression Immunity Immunologic Memory Individual Infection Kinetics Label Lead Lymphatic Endothelial Cells Memory Methods Modeling Molecular Mus Oligonucleotides Organ Peripheral Process Proteins Publishing Regimen Resistance Reticular Cell Route Source Stromal Cells System T cell response T memory cell T-Lymphocyte Techniques Time Tissues Vaccinated Vaccination Vaccines Viral Viral Antigens Virus Virus Diseases body system cell type functional outcomes improved lymph nodes novel novel strategies nuclease programs single cell mRNA sequencing uptake vaccination strategy vaccine formulation

Accounting Address Adjuvant Antigen Presentation Antigens Archives Attenuated Attenuated Vaccines CD8-Positive T-Lymphocytes Cell Communication Cell Death Cells Cellular Immunity DNA Data Dendritic Cells Devices Gene Expression Immunity Immunologic Memory Individual Infection Kinetics Label Lead Lymphatic Endothelial Cells Memory Methods Modeling Molecular Mus Oligonucleotides Organ Peripheral Process Proteins Publishing Regimen Resistance Reticular Cell Route Source Stromal Cells System T cell response T memory cell T-Lymphocyte Techniques Time Tissues Vaccinated Vaccination Vaccines Viral Viral Antigens Virus Virus Diseases body system cell type functional outcomes improved lymph nodes novel novel strategies nuclease programs single cell mRNA sequencing uptake vaccination strategy vaccine formulation

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项目摘要

Project Summary Live attenuated vaccinations generate both humoral and cellular immune memory, accounting for much of the increased duration of protective immune memory. As increased protective immune memory to live attenuated vaccines is of critical importance, understanding the mechanisms of this increased protective immune memory is essential to improve current vaccines. To this end, we and others have demonstrated that antigens derived from infectious viral infections persist in the host for extended periods of time, well beyond the time in which the infection is cleared from the host. Our lab has specifically identified that antigens derived from both vaccination and viral infections persist or are archived by the host lymphatic endothelial cells LECs, identifying the source of archived antigens. We have published that this archived antigen maintains a more effector like pool of antigen specific memory cells which enhances the clearance of a secondary infectious challenge. Thus, identification of key mechanisms involved in antigen archiving during vaccination is critical for our understanding of enhanced protective immunity to vaccination. To better understand the mechanisms of antigen archiving we have developed a “molecular tracking device” that leverages single-cell mRNA sequencing to track the distribution, acquisition, and retention of antigen in the lymph node and other organs. This project will elucidate the unique mechanisms behind antigen archiving, how multiple un-related infections contribute to the kinetics of archived antigens and memory boosting, and the potential cell types in other tissues that may also contribute to antigen archiving.

项目摘要现场衰减疫苗接种会产生体液和细胞免疫组记忆，占大部分受保护免疫记忆的持续时间增加。随着受保护的免疫记忆力增加而导致活跃疫苗至关重要，了解这种受保护的免疫记忆的机制对于改善当前疫苗至关重要。为此，我们和其他人证明了抗原得出从传染性病毒感染中，宿主的长时间持续存在，远远超出了从宿主清除感染。我们的实验室专门确定了抗原源自这两者疫苗接种和病毒感染持续存在或被宿主淋巴内皮细胞LEC存档，以识别存档抗原的来源。我们已经发表了该存档的抗原具有更大的效应器抗原特异性记忆细胞池，可增强次级感染挑战的清除。那，识别疫苗接种期间抗原归档的关键机制对我们来说至关重要了解增强的保护性免疫对疫苗接种。更好地了解抗原归档我们已经开发了一种利用单细胞mRNA的“分子跟踪装置” 测序以跟踪抗原在淋巴结和其他器官中的分布，采集和保留。该项目将阐明抗原归档背后的独特机制，多种无关感染有助于存档抗原和内存增强的动力学，以及其他潜在的细胞类型也可能有助于抗原归档的组织。