Targeted antigens for novel strategies of vaccination

新疫苗接种策略的靶向抗原

• 批准号: 6805040
• 负责人: STEPHEN M HEDRICK
• 金额: $ 30.4万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6805040
• 关键词: Paramyxovirus; active immunization; antibody specificity; antigen antibody reaction; antigen presentation; biotechnology; cell surface receptors; dendritic cells; flow cytometry; genetic manipulation; helper T lymphocyte; hybridomas; laboratory mouse; leukocyte activation /transformation; molecular cloning; molecular shape; polymerase chain reaction; receptor binding; receptor mediated endocytosis; synthetic antigens; synthetic protein; vaccine development; vaccinia virus; viral vaccines

DESCRIPTION (provided by applicant): The process of immunization involves antigen uptake and processing by professional antigen presenting cells (APCs), activation of APCs, and migration of antigen-bearing cells to lymphoid organs. This in turn can result in the activation of T lymphocytes. This process is dependent upon the presence of inflammatory signals usually provided by microbial pattern recognition. Previous work has shown that antibody molecules provide an ideal delivery vehicle for antigen presentation and vaccination. Antibodies can efficiently direct an associated antigen to a particular cellular subset, such as dendritic cells, and simultaneously fulfill the requirement for cellular activation. Depending on the type of dendritic subset targeted, a prediction is that a Th1 or Th2-1ike responses will result. In addition, by altering the molecular form of the antigenic Ig molecules, and specifying a target receptor, antigen may be directed into either the MHC class I or MHC class II antigen presentation pathways. This proposal describes experiments to establish the basic principles of antibody-directed antigen presentation leading to immunization. More importantly, the experiments will lead to the design of a new generation of vaccines capable of directing the class and thus the effectiveness of immune responses.

描述（由申请方提供）：免疫过程涉及专职抗原呈递细胞（APC）的抗原摄取和加工、APC的活化以及携带抗原的细胞迁移至淋巴器官。这反过来又会导致T淋巴细胞的激活。这个过程取决于炎症信号的存在，通常由微生物模式识别提供。先前的工作已经表明，抗体分子为抗原呈递和疫苗接种提供了理想的递送载体。抗体可以有效地将相关抗原导向特定的细胞亚群，如树突状细胞，同时满足细胞活化的要求。根据靶向树突细胞亚群的类型，预测将产生Th1或Th2样应答。此外，通过改变抗原性IG分子的分子形式，并指定靶受体，抗原可被引导进入MHC I类或MHC II类抗原呈递途径。 本提案描述了建立抗体导向的抗原呈递导致免疫的基本原理的实验。更重要的是，这些实验将导致新一代疫苗的设计，能够指导类，从而有效的免疫反应。