Genetically-Programmed APC Vaccines Against Viruses

描述（由申请人提供）：在R21基金（AI 49771：转基因B细胞免疫原）的支持下，我们使用甲型流感病毒作为模型系统开发了一种基于抗原呈递细胞（APC）的疫苗。针对CD 8 T细胞记忆应答的研究表明，保护作用是由具有高CD 62 L表达的CD 8 T细胞介导的。这些细胞被称为中央记忆T细胞。现在提出了关于体内保护相关性的这一发现，作为理解通过疫苗接种诱导保护性记忆CD 8 T细胞的要求的新实验的基础。我们希望测试的假设是，通过遗传APC疫苗成功编程的中央记忆CD 8 T细胞诱导可能受到一系列一般性质的考虑，如剂量和引发和遇到病原体之间的间隔，与环境如树突状细胞和IL-15的相互作用，以及CD 62 L作为特征基因的关键表型特征的存在。 我们的目标是进一步使用新开发的APC疫苗接种系统作为原理证明，以了解针对3类病毒病原体产生保护性中央记忆CD 8 T细胞的要求。我们的研究的重要性还在于，新的疫苗接种方法虽然建立在基本公理疫苗接种->免疫->保护的基础上，但其目的是诱导对疾病的保护，从而为疫苗控制旧的或新出现的传染病设定了新的目标。我们相信，我们的研究将在开发一种替代方法，有效地接种疫苗，针对甲型流感病毒使用新的APC疫苗的方法的影响。

DESCRIPTION (provided by applicant): Under the aegis of an R21 grant (AI49771: Transgenic B cell immunogens), we developed an antigen-presenting cell (APC)-based vaccine using the influenza A virus as a model system. Studies focused on CD8 T cell memory responses revealed that protection is mediated by CD8 T cells with high CD62L expression. These are referred to as central memory T cells. This finding on the correlate of protection in vivo is now proposed as the basis for a new experiment to understand the requirements to induce protective memory CD8 T cells by vaccination. The hypothesis we wish to test is that successful programming by a genetic APC vaccine of central memory CD8 T cell induction may be subject to a series of considerations of general nature such as dose and interval between priming and encounter with the pathogen, the interaction with the environment such as dendritic cells and IL-15, and the presence of CD62L as a key phenotypic feature of the signature gene. Our objective is to further use the newly developed APC vaccination system as a proof of principle to understand the requirements for the generation of protective central memory CD8 T cells against a category 3 viral pathogen. The importance of our studies is also that the new vaccination approach while built on the cardinal axiom Vaccination--> Immunity--> Protection is intended at inducing protection against disease, hence setting a new target for vaccine-directed control of old or emerging infectious diseases. We believe that our studies will have implications in the development of an alternative approach to effectively vaccinate against influenza A virus using novel APC vaccine approach.