DEVELOPMENT AND TESTING OF NEW TUBERCULOSIS VACCINES

描述：（改编自申请人的摘要）结核分枝杆菌， 结核病的主要病原体，感染了世界上三分之一的人口 每年造成300万人死亡，成为世界上最主要的疾病。 死于单一传染源它是导致疾病的主要原因， 艾滋病患者的死亡率，特别是在世界上的发展中国家。 全球迅速出现对所用主要抗生素耐药的菌株 治疗结核病对公众健康构成严重威胁。最高 防治结核病的优先事项是研制一种疫苗， 比现在的卡介苗更有效一种比 卡介苗对人类健康的影响几乎比任何其他疫苗都大。 在抗击传染病的斗争中取得了可以想象的进展。研究从 这个实验室在目前的赠款下完成，建立了重要性， 主要胞外蛋白。结核病在诱导细胞介导的 和保护性免疫在豚鼠肺结核模型， 高度易感的物种，发展疾病与人类非常相似 结核目前赠款下的研究也成功地发展了 以天然形式高水平表达和分泌主要M. 结核病细胞外蛋白在一个非致病性的快速增长， 异源宿主，允许分离和纯化100 mg量的 重组耻垢分枝用于疫苗研究的结核病细胞外蛋白。在这 在申请拨款时，我们寻求建立在知识和经验的基础上， 以前的研究开发了一种比BCG更有效的疫苗， 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M.结核 细胞外和细胞相关蛋白质和新的非活颗粒 配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.