li Suppression-enhanced HIV DNA Vaccine

li 抑制增强型 HIV DNA 疫苗

• 批准号: 6589659
• 负责人: MINZHEN XU
• 金额: $ 35.41万
• 依托单位: ANTIGEN EXPRESS, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6589659
• 关键词: AIDS vaccines; HIV envelope protein gp120; MHC class II antigen; T lymphocyte; cell proliferation; dendritic cells; interferon gamma; invariant chain; laboratory mouse; leukocyte activation /transformation; molecular cloning; recombinant DNA; transfection; vaccine development; vector vaccine

DESCRIPTION (provided by applicant): Antigen Express scientists have discovered that cells expressing MHC class II molecules in the absence of the MHC class II-associated Ii protein can act as effective cellular vaccines. Cells with the MHC class II+/Ii-phenotype simultaneously present endogenously synthesized antigens by both MHC class I and class II molecules to CD8+ and CD4+ T cells, respectively. When the Ii protein does not block the MHC class II molecules at synthesis, the epitope pool available for MHC class I is also available for presentation by MHC class II molecules, leading to the creation of very potent vaccine cells. In this SBIR, we will use our Ii-suppression technology to augment the efficacy of HIV DNA vaccines. We will: 1) clone the HIV gp120 gene into vectors containing our Ii-reverse gene construct. Dendritic cells that take up the vector will then both synthesize gp120 and form the MHC class II+/Ii-phenotype; 2) identify optimal routes of inoculation and delivery agents for the in vivo transfection of lymph node lymphocytes and dendritic cells and, 3) characterize the in vivo ability of Ii-RGC/gp120 containing vectors versus gp120 alone to generate gp120-specific T cell proliferation and gp120-specific CTL activity. Our experiments will establish the potential utility of developing Ii-RGC/gp120 DNA vectors as HIV vaccines in the clinic. In a Phase II program Ii-RGC/gp120 DNA vaccines will be tested in non-human primates for the induction of a protective immune response against pathogenic HIV infection.

描述(申请人提供)：抗原快递科学家已经发现，在缺乏MHC II类相关II蛋白的情况下表达MHC II类分子的细胞可以作为有效的细胞疫苗。具有MHC II+/II-表型的细胞同时向CD8+和CD4+T细胞递送由MHC I类和II类分子内源性合成的抗原。当II蛋白在合成时不阻止MHC II类分子时，MHC I类分子可用的表位池也可以由MHC II类分子呈现，从而产生非常有效的疫苗细胞。在这项SBIR中，我们将使用我们的II-抑制技术来增强HIV DNA疫苗的效力。我们将：1)将HIV gp120基因克隆到含有我们的II-反向基因构建的载体中。然后，携带载体的树突状细胞将合成gp120并形成MHC II+/II-表型；2)确定淋巴淋巴细胞和树突状细胞体内转染的最佳接种和递送剂途径；3)鉴定II-RGC/gp120载体与单独gp120相比在体内产生gp120特异性T细胞增殖和gp120特异性CTL活性的能力。我们的实验将为开发II-RGC/gp120 DNA载体作为HIV疫苗在临床上的应用奠定基础。在第二阶段计划中，将在非人类灵长类动物身上测试II-RGC/gp120 DNA疫苗，以诱导对致病性艾滋病毒感染的保护性免疫反应。