li Suppression-enhanced HIV DNA Vaccine

描述（由申请人提供）：抗原表达科学家发现，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 -表型的细胞同时将MHC I类和MHC II类分子内源性合成的抗原分别呈递给CD8+和CD4+ T细胞。当Ii蛋白在合成时不能阻断MHC Ii类分子时，MHC I类可用的表位库也可用于MHC Ii类分子的呈递，从而产生非常有效的疫苗细胞。在这个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ii -逆转录基因构建体的载体中。接受载体的树突状细胞将合成gp120并形成MHC II+/ II型表型；2)确定体内转染淋巴结淋巴细胞和树突状细胞的最佳接种途径和递送剂；3)表征含Ii-RGC/gp120载体相对于单独gp120载体产生gp120特异性T细胞增殖和gp120特异性CTL活性的体内能力。我们的实验将建立Ii-RGC/gp120 DNA载体作为HIV疫苗在临床中的潜在效用。在II期项目中，II - rgc /gp120 DNA疫苗将在非人类灵长类动物中进行试验，以诱导针对致病性HIV感染的保护性免疫反应。

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.