Guinea pig model for TB vaccine evaluations

描述（由申请方提供）：在过去几年中，在鉴定可能用于人类结核病预防或免疫治疗的新候选疫苗方面取得了重大进展。该项目的目的是选择这些候选疫苗中的一些，并进行长期有效性和安全性评估，以确定哪些疫苗最有效。使用的动物模型将是豚鼠中的低剂量气雾剂激发，鉴于其对感染的易感性和免疫病理学与人类疾病的相似性，该动物提供了严格的试验。要检验的中心假设是，不同的疫苗，鉴于其免疫靶点可能不同的数据，可能在调节、延迟或预防疾病过程发展的能力方面表现不同。为了促进这一分析，我们将使用我们最近定义的感染豚鼠肺部肉芽肿过程的四个离散阶段作为模板，拟议的研究是漫长的，而且相当昂贵，但应该提供一个基本框架，在此基础上，新的结核病疫苗的有效性和安全性测试的标准化程序可以基于。

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.