li Suppression-enhanced HIV DNA Vaccine

描述（由申请人提供）：Antigen Express科学家发现，在不存在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类+/II-表型的细胞同时通过MHC I类和II类分子分别向CD 8+和CD 4 + T细胞呈递内源性合成的抗原。 当Ii蛋白在合成时不阻断MHC II类分子时，可用于MHC I类的表位库也可用于由MHC II类分子呈递，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疫苗的功效。 我们将：1）将HIV gp 120基因克隆到含有我们的Ii-反向基因构建体的载体中。 然后，摄取载体的树突细胞将合成gp 120并形成MHC II类+/II类-表型; 2）鉴定用于体内转染淋巴结淋巴细胞和树突细胞的接种和递送剂的最佳途径，3）表征含有Ii-RGC/gp 120的载体相对于单独的gp 120产生gp 120特异性T细胞增殖和gp 120特异性T细胞增殖的体内能力，特异性CTL活性。 我们的实验将建立开发Ii-RGC/gp 120 DNA载体作为HIV疫苗在临床上的潜在效用。 在II期计划中，将在非人灵长类动物中测试Ii-RGC/gp 120 DNA疫苗诱导针对病原性HIV感染的保护性免疫应答。

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.