Genetically-Programmed APC Vaccines Against Viruses

针对病毒的基因编程 APC 疫苗

• 批准号: 7008599
• 负责人: MAURIZIO ZANETTI
• 金额: $ 30.13万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7008599
• 关键词: antigen presenting cell; cell transplantation; cytotoxic T lymphocyte; influenza vaccines; vaccine development; vector vaccine; viral vaccines

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.

描述（由申请人提供）：在 R21 资助（AI49771：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 CD8 T 细胞记忆反应的研究表明，保护作用是由高 CD62L 表达的 CD8 T 细胞介导的。这些被称为中央记忆 T 细胞。这一关于体内保护相关性的发现现在被提议作为一项新实验的基础，以了解通过疫苗接种诱导保护性记忆 CD8 T 细胞的要求。我们希望测试的假设是，中央记忆 CD8 T 细胞诱导的基因 APC 疫苗的成功编程可能受到一系列一般性质的考虑，例如剂量和启动与接触病原体之间的间隔、与病原体的相互作用。树突状细胞和 IL-15 等环境，以及 CD62L 的存在作为特征基因的关键表型特征。 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 类病毒病原体生成保护性中央记忆 CD8 T 细胞的要求。我们研究的重要性还在于，新的疫苗接种方法建立在疫苗接种-->免疫-->保护基本公理的基础上，旨在诱导针对疾病的保护，从而为疫苗定向控制旧有或新出现的传染病设定了新目标疾病。我们相信，我们的研究将对开发一种使用新型 APC 疫苗方法有效接种甲型流感病毒疫苗的替代方法产生影响。