DEVELOPMENT AND TESTING OF NEW TUBERCULOSIS VACCINES

描述：(改编自申请者摘要)结核分枝杆菌， 结核病的主要病原体，感染了世界三分之一的人口 每年导致300万人死亡，使其成为世界上最主要的 死于单一感染性病原体。它是疾病的主要原因之一， 艾滋病患者的死亡，特别是在世界发展中国家。 对所使用的主要抗生素产生抗药性的菌株在全球迅速出现 治疗结核病对公众健康构成严重威胁。最高的 与结核病作斗争的当务之急是开发一种疫苗， 比目前的疫苗-卡介苗更有效。一种比疫苗更有效的疫苗 卡介苗对人类健康的影响几乎比其他任何疫苗都要大。 可以想象在抗击传染病方面的发展。研究来自 在目前的拨款下完成的这一实验室确定了 结核分枝杆菌主要胞外蛋白诱导细胞介导性 和保护性免疫在豚鼠肺结核模型中的作用 高度敏感的物种，其疾病发展与人类极其相似 肺结核。目前拨款下的研究也成功地开发了 原生高效表达和分泌M。 结核杆菌胞外蛋白在非致病性中的快速生长 异源宿主，允许分离和提纯100毫克量的 用于疫苗研究的重组结核分枝杆菌胞外蛋白。在这 拨款申请，我们寻求建立在获得的知识和经验 以前的研究开发出一种比卡介苗更有效的疫苗，在高度 相关豚鼠模型。我们寻求开发和测试活的重组 包括表达主要结核分枝杆菌的重组卡介苗的疫苗 细胞外和细胞相关蛋白和新的非活颗粒物 制成脂质体和微球的疫苗。

DESCRIPTION: (Adapted from Applicant's Abstract) Mycobacterium tuberculosis, the primary agent of tuberculosis, infects one-third of the world's population and kills 3 million people annually, making it the world's leading cause of death from a single infectious agent. It is a leading cause of disease and death in AIDS patients, particularly in the developing nations of the world. The rapid global emergence of strains resistant to the major antibiotics used to treat tuberculosis poses a serious threat to public health. The highest priority in the fight against tuberculosis is the development of a vaccine that is more efficacious than the current vaccine - BCG. A vaccine more potent than BCG would have an impact on human health greater than virtually any other conceivable development in the fight against infectious diseases. Studies from this laboratory completed under the current grant established the importance of major extracellular proteins of M. tuberculosis in inducing both cell-mediated and protective immunity in the guinea pig model of pulmonary tuberculosis, a highly susceptible species that develops disease remarkably similar to human tuberculosis. Studies under the current grant also succeeded in developing technology for high level expression and secretion in native form of major M. tuberculosis extracellular proteins in a nonpathogenic rapidly growing heterologous host, allowing isolation and purification of 100 mg quantities of recombinant M. tuberculosis extracellular proteins for vaccine studies. In this grant application, we seek to build on the knowledge and experience gained in previous studies to develop a vaccine more potent than BCG in the highly relevant guinea pig model. We seek to develop and test live recombinant vaccines including recombinant BCG expressing major M. tuberculosis extracellular and cell-associated proteins and new non-live particulate vaccines formulated as liposomes and microspheres.