Genetically-Programmed APC Vaccines Against Viruses

针对病毒的基因编程 APC 疫苗

基本信息

批准号：
7173396
负责人：
MAURIZIO ZANETTI
金额：
$ 29.3万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-02-01 至 2009-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7173396
关键词：
APC Vaccine Address Adoptive Transfer Aerosols Antigen Presentation Antigen-Presenting Cells Antigens B-Lymphocytes Biological Models Bioterrorism Bone Marrow CD8B1 gene Categories Cells Cytoprotection Dendritic Cells Development Disease Dose Emerging Communicable Diseases Environment Epidemic Family Generations Genes Genetic Grant Immunity Immunization Influenza Influenza A virus Interleukin-15 Kinetics Knowledge L-Selectin Maintenance Mediastinal Mediating Memory Mus Nature Nucleoproteins Orthomyxoviridae Phase Play RNA Viruses Role SELL gene Series Severity of illness Stromal Cells System T memory cell T-Lymphocyte T-Lymphocyte Epitopes Technology Testing Thinking Time Today Transgenic Organisms United States National Institutes of Health Vaccinated Vaccination Vaccines Viral Viral Vaccines Virulent Virus Virus Diseases base cytokine design frontier genetic vaccine in vivo influenzavirus killings knock-down novel novel vaccines pandemic disease pandemic influenza pathogen programs research study respiratory response vaccinology young adult

项目摘要

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）：根据R21赠款的敬业（AI49771：转基因B细胞免疫原），我们使用流感病毒作为模型系统开发了一种基于抗原的呈现抗原呈递细胞（APC）的疫苗。针对CD8 T细胞记忆反应的研究表明，保护是由CD62L表达高的CD8 T细胞介导的。这些称为中央记忆T细胞。现在提出了有关在体内保护的相关性的发现，作为新实验的基础，以了解通过疫苗接种诱导保护性记忆CD8 T细胞的要求。我们希望检验的假设是，通过中央记忆的遗传APC疫苗CD8 T细胞诱导的遗传APC疫苗可能会受到一系列对一般性质的考虑，例如剂量和与病原体的启动和相遇之间的间隔，与环境的相互作用，与树突状细胞和IL-15的环境的相互作用，例如CD62L，以及CD62L的存在，作为CD62L的存在，作为关键的成立特征。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的证明，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。我们的研究的重要性还在于，建立在基于基本公理疫苗接种的新疫苗接种方法 - >免疫 - >保护旨在诱导防止疾病的保护，因此为疫苗定向的旧或新兴传染病的控制设定了新的目标。我们认为，我们的研究将对采用新型APC疫苗方法有效疫苗接种的替代方法具有影响。