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.

项目摘要 减毒活疫苗产生体液和细胞免疫记忆，占大部分的免疫记忆。 保护性免疫记忆的持续时间增加。由于增加了对减毒活疫苗的保护性免疫记忆 疫苗是至关重要的，了解这种增加保护性免疫记忆的机制， 对改进现有疫苗至关重要。为此，我们和其他人已经证明， 感染性病毒感染在宿主体内持续很长一段时间，远远超过 感染从宿主中清除。我们的实验室已经特别鉴定出 疫苗接种和病毒感染持续存在或由宿主淋巴管内皮细胞LEC存档， 存档抗原的来源。我们已经发表，这种存档的抗原保持了更像效应子的特性， 抗原特异性记忆细胞库，其增强二次感染性攻击的清除。因此，在本发明中， 确定疫苗接种过程中抗原存档的关键机制对我们的研究至关重要。 增强对疫苗接种的保护性免疫的认识。为了更好地理解 抗原存档我们已经开发了一种“分子跟踪装置”，利用单细胞mRNA 测序以追踪抗原在淋巴结和其他器官中的分布、获得和保留。 这个项目将阐明抗原存档背后的独特机制， 有助于存档抗原和记忆增强的动力学，以及其他细胞中的潜在细胞类型。 也可能有助于抗原存档的组织。