Molecular tracking of antigen following vaccination

疫苗接种后抗原的分子追踪

• 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
• 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

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.

项目概要 减毒活疫苗产生体液和细胞免疫记忆，占大部分 保护性免疫记忆的持续时间随着保护性免疫记忆的增加而减弱。 疫苗至关重要，了解这种增加保护性免疫记忆的机制 为此，我们和其他人已经证明了抗原的来源。 传染性病毒感染在宿主体内持续存在很长一段时间，远远超出了感染的时间 我们的实验室已明确鉴定出来自这两种病毒的抗原。 疫苗接种和病毒感染持续存在或由宿主淋巴内皮细胞 LEC 存档，从而识别 我们已经发布了存档抗原的来源，该存档抗原保留了一个更像效应器的东西。 抗原特异性记忆细胞库增强了二次感染攻击的清除能力。 识别疫苗接种期间抗原归档所涉及的关键机制对于我们的研究至关重要 了解增强疫苗接种的保护性免疫力的机制。 抗原归档 我们开发了一种利用单细胞 mRNA 的“分子追踪装置” 测序以跟踪抗原在淋巴结和其他器官中的分布、获取和保留。 该项目将阐明抗原存档背后的独特机制，以及多种不相关的感染如何 有助于存档抗原的动力学和记忆增强，以及其他潜在的细胞类型 也可能有助于抗原归档的组织。