DEVELOPMENT AND TESTING OF NEW TUBERCULOSIS VACCINES

新型结核疫苗的开发和测试

• 批准号: 6534017
• 负责人: MARCUS AARON HORWITZ
• 金额: $ 51.5万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-04-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6534017
• 关键词: AIDS; Mycobacterium bovis; Mycobacterium tuberculosis; active immunization; bacterial antigens; bacterial proteins; cellular immunity; disease /disorder model; epitope mapping; guinea pigs; live vaccine; opportunistic infections; recombinant proteins; tuberculosis; tuberculosis vaccines; vaccine development

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.

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，感染世界三分之一的人口 每年造成 300 万人死亡，使其成为世界上造成 死于单一传染源。它是疾病的主要原因，并且 艾滋病患者的死亡，特别是在世界发展中国家。 全球对主要抗生素产生耐药性的菌株迅速出现 治疗结核病对公众健康构成严重威胁。最高的 防治结核病的首要任务是开发一种疫苗 比目前的疫苗——卡介苗更有效。比疫苗更有效的疫苗 卡介苗对人类健康的影响几乎比任何其他药物都要大 在防治传染病方面取得了可想而知的发展。研究来自 该实验室是在当前赠款下完成的，它确立了以下方面的重要性： 结核分枝杆菌的主要细胞外蛋白诱导细胞介导的 肺结核豚鼠模型中的保护性免疫和保护性免疫 高度易感的物种，其疾病与人类非常相似 结核。目前资助下的研究也成功地开发了 技术以天然形式高水平表达和分泌主要分枝杆菌。 结核细胞外蛋白在非致病性中快速生长 异源宿主，允许分离和纯化 100 mg 数量的 用于疫苗研究的重组结核分枝杆菌胞外蛋白。在这个 拨款申请中，我们力求以在以下领域获得的知识和经验为基础： 先前的研究旨在开发一种比卡介苗更有效的疫苗 相关豚鼠模型。我们寻求开发和测试活重组体 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以及新的非活性颗粒 配制为脂质体和微球的疫苗。