Guinea pig model for TB vaccine evaluations

描述(由申请人提供)：在过去几年中，在确定可能用于预防或免疫治疗人类结核病的新候选疫苗方面取得了重大进展。这一拟议项目的目的是从这些候选疫苗中挑选几个，并进行长期的疗效和安全性评估，以确定哪些是最健壮的。将要使用的动物模型将是在豚鼠身上进行的低剂量气雾剂攻击，这种动物提供了严格的测试，因为它对感染的敏感性和免疫病理学对人类疾病的相似之处。需要测试的中心假设是，鉴于不同疫苗的免疫靶点可能不同，不同的疫苗在调节、延迟或防止疾病过程发展的能力方面可能表现不同。为了促进这一分析，我们将使用我们最近对受感染豚鼠肺部肉芽肿过程的四个离散阶段的定义作为模板，拟议的研究既冗长又不可避免地昂贵，但应该提供一个基本框架，用于新结核病疫苗的有效性和安全性测试的标准化程序。

DESCRIPTION (provided by applicant): Significant progress has been made over the past few years in identifying new vaccine candidates that could potentially be used for the prevention or immunotherapy of tuberculosis in human beings. The purpose of this proposed project is to take a select few of these vaccine candidates and perform longer term efficacy and safety evaluations to see which are the most robust. The animal model to be used will be the low dose aerosol challenge in the guinea pig, an animal which provides a stringent test given its susceptibility to infection and similarities in immunopathology to human disease. The central hypothesis to be tested will be that different vaccines, given data that their immunologic targets may differ, may behave differently in their ability to modulate, delay, or prevent the development of the disease process. To facilitate this analysis, we will use as a template our recent definition of four discrete phases of the granulomatous process in the lungs of infected guinea pigs, The proposed studies are lengthy, and unavoidably expensive, but should provide a basic framework upon which a standardized procedure for efficacy and safety testing of new tuberculosis vaccines can be based.