Response Therapies for MDR-TB

描述(由申请人提供)：对RFA 05-019的答复来自科罗拉多州立大学分枝杆菌研究实验室、西雅图传染病研究所和科罗拉多州洛夫兰的Mycos Research。这项申请的目的具有应用的科学基础，包括优先考虑有前景的新药，以及有望作为暴露后疫苗的分枝杆菌抗原，以处理个人故意接触结核分枝杆菌的分离株，这是一种C类病原体，可能对所有已知的常规使用的结核病药物产生抗药性。几种前景看好的先导化合物以及PA-824等新的研究药物最近已经在CSU进行了测试，并将在该计划中针对MDR菌株进行进一步的探索。此外，三家领先的制药公司都表示愿意在这一计划中进行合作，并提供已知对药物敏感的结核分枝杆菌有活性的其他化合物。在平行研究中，我们还将利用我们在结核病疫苗研究方面经过验证的专业知识，根据本提案中详细说明的表明可以实现这一目标的早期结果，处理更困难的问题，即开发一种快速有效的暴露后疫苗。这些都是基于蛋白质的，此外，我们还将测试为有效的TH1反应而选择的新一代佐剂。一旦确定了新的候选者，他们将根据我们的结果与新的化疗方案一起进行测试。安全测试问题、毒理学测试和导致GMP生产的工艺开发也计划在这一拟议计划的后期阶段进行。

DESCRIPTION (provided by applicant): This response to RFA 05-019 is from the Mycobacteria Research Laboratories at Colorado State University, the Infectious Disease Research Institute in Seattle, and Mycos Research, Loveland, Colorado. The purpose of this application has an applied scientific basis and consists of prioritization of new promising drugs, as well as mycobacterial antigens that have promise as post-exposure vaccines, to deal with a deliberate exposure of individuals to an isolate of Mycobacterium tuberculosis, a Class C pathogen, that might potentially be resistant to all known conventionally used TB drugs. Several promising lead compounds as well new investigational drugs such as PA-824 have recently been tested at CSU and will be explored further in this program against MDR strains. In addition, three leading pharmaceutical companies have all expressed their willingness to collaborate in this program and to provide additional compounds already known to be active against drug sensitive M. tuberculosis. In parallel studies we will also lend our proven expertise in TB vaccine research to deal with the more difficult issue of developing a rapidly active post-exposure vaccine, based upon early results detailed in this proposal indicating that this can be achieved. These are protein based, and in addition we will test a new generation of adjuvants selected for potent TH1 responses. Once new candidates are identified they will be tested in conjunction with new chemotherapy regimens based upon our results. Safety testing issues, toxicology testing, and process development leading to GMP production are also planned for the later stages of this proposed program.