DEVELOPMENT OF A RECOMBINANT TUBERCULOSIS VACCINE

重组结核疫苗的开发

• 批准号: 6283483
• 负责人: STEVEN GREGORY REED
• 金额: $ 2.6万
• 依托单位: CORIXA CORPORATION
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-05 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6283483
• 关键词: Mycobacterium tuberculosis; synthetic vaccines; tuberculosis; tuberculosis vaccines; vaccine development

As part of a comprehensive tuberculosis vaccine development effort over the past five years, we have identified more than 80 antigen genes from Mycobacterium tuberculosis (Mtb). From these genes, several vaccine candidates have been chosen on the basis of 1) their recognition by T cells form healthy PPD+ donors, and 2) preclinical studies in mice showing Th1 and CTL responses. Our current efforts, for which we seek matching funds, involve the optimization of vaccine constructs and delivery systems in animal models to maximize protective efficacy. Using the priority Mtb antigens we have identified we will produce poly-proteins with high expression levels in recombinant systems suitable for manufacture. We will use these protein antigens with state-of-the-art adjuvants, already tested in the clinic, along with delivery systems chosen to maximize T cell responses. We will focus on vaccine studies in the guinea pig and primate systems, as well as use mice to characterize immune responses induced by the experimental vaccines.

作为过去五年全面结核病疫苗开发工作的一部分，我们已经从结核分枝杆菌（Mtb）中确定了80多个抗原基因。从这些基因中，选择了几种候选疫苗，其基础是1)它们被来自健康PPD+供体的T细胞识别，以及2)在小鼠中显示Th1和CTL反应的临床前研究。我们目前的努力包括在动物模型中优化疫苗结构和递送系统，以最大限度地提高保护效果，为此我们正在寻求配套资金。利用我们已经确定的优先Mtb抗原，我们将在适合生产的重组系统中生产高表达水平的多蛋白。我们将使用这些蛋白抗原和最先进的佐剂，这些佐剂已经在临床测试过，同时选择递送系统来最大化T细胞反应。我们将专注于在豚鼠和灵长类动物系统中的疫苗研究，以及用小鼠来表征实验疫苗诱导的免疫反应。