Human T Cell Antigens of Mycobacterium tuberculosis

描述(申请人提供)：基于人类T细胞反应和动物保护，我们已经确定了几种新的结核病疫苗候选抗原。那些既能从PPD阳性的健康捐赠者的PBMC中诱导Th1反应，又能在啮齿动物模型中保护的药物被优先考虑。已经开发了几种动物模型来评估疫苗的效力，目前正在用于进一步确定候选疫苗和佐剂/递送系统的特征。我们建议通过在临床和地理上不同的人群中使用最先进的免疫学分析方法，通过广泛的测试来扩大对候选疫苗抗原的评估。本节将提供有关在感染不同分离株的遗传不同人群中保存抗原的重要信息。这些研究还将为定义保护的关键免疫学相关因素奠定基础。同时，我们将在啮齿动物模型中使用优先抗原和疫苗配方进行免疫原性研究。我们还将对AS02a中使用Mtb72f免疫的人类志愿者的免疫反应进行详细分析，AS02a是第一种进入临床试验的明确结核病疫苗。最后，我们将在感染和疾病的啮齿动物模型中测试抗原/疫苗配方。到资助期结束时，我们将确定第二种候选疫苗进入临床试验。

DESCRIPTION (provided by applicant): We have identified several new TB vaccine candidate antigens based on human T cell responses and animal protection. Priority has been given to those that both elicit a Th1 response from PBMC from PPD positive healthy donors and protect in rodent models. Several animal models have been developed to evaluate vaccine efficacy and are currently being used to further characterize vaccine candidates and adjuvant/delivery systems. We propose to expand the evaluation of candidate vaccine antigens through extensive testing in clinically and geographically diverse populations, using state of the art immunological assays. This section will provide important information on conservation of antigens in genetically diverse populations infected with diverse isolates. These studies will also lay the foundation for definition of key immunological correlates of protection. In parallel, we will perform immunogenicity studies using priority antigens and vaccine formulations in rodent models. We will also perform detailed analysis of the immune responses of human volunteers immunized with Mtb72f in AS02A, the first defined TB vaccine to enter clinical trials. Finally, we will test antigens/vaccine formulations in rodent models of infection and disease. By the end of the funding period, we will have defined a second vaccine candidate for entry into clinical trials.