Molecular tracking of antigen following vaccination

项目摘要 减毒活疫苗产生体液和细胞免疫记忆，占很大一部分 增加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活体减弱 疫苗至关重要，要了解这种增强保护性免疫记忆的机制 对改进目前的疫苗至关重要。为此，我们和其他人证明了抗原来源于 传染性病毒感染在宿主体内持续很长一段时间，远远超过 从宿主身上清除感染。我们的实验室已经明确地确定了来自这两种来源的抗原 疫苗接种和病毒感染持续存在或被宿主淋巴管内皮细胞存档，识别 存档抗原的来源。我们已经发表了这种存档的抗原维持着更多的效应器，比如 抗原特异性记忆细胞池，可增强对次级感染挑战的清除。因此， 识别疫苗接种过程中涉及的抗原存档的关键机制对我们的 对加强疫苗接种保护性免疫的认识。为了更好地了解 抗原存档我们已经开发出一种利用单细胞信使核糖核酸的“分子跟踪装置” 测序跟踪抗原在淋巴结和其他器官中的分布、获取和滞留的序列。 该项目将阐明抗原存档背后的独特机制，以及多种无关感染 有助于存档抗原和记忆增强的动力学，以及其他可能的细胞类型 也可能有助于抗原存档的组织。

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.