DEVELOPMENT OF A RECOMBINANT TUBERCULOSIS VACCINE

在过去的五年中，作为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）中鉴定了80多个抗原基因。从这些基因中，基于1）它们被来自健康PPD+供体的T细胞识别，和2）在小鼠中显示Thl和CTL应答的临床前研究，已经选择了几种候选疫苗。我们目前的努力，我们寻求匹配的资金，涉及优化疫苗结构和动物模型中的输送系统，以最大限度地提高保护效力。使用我们已经鉴定的优先Mtb抗原，我们将在适于制造的重组系统中产生具有高表达水平的多蛋白。我们将使用这些蛋白质抗原与最先进的佐剂，已经在临床上测试，沿着输送系统选择，以最大限度地提高T细胞的反应。我们将专注于豚鼠和灵长类动物系统的疫苗研究，以及使用小鼠来表征实验疫苗诱导的免疫反应。

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.