Human T Cell Antigens of Mycobacterium tuberculosis

描述（由申请人提供）：我们已经基于人T细胞应答和动物保护鉴定了几种新的TB疫苗候选抗原。优先考虑那些既能从PPD阳性健康供体的PBMC中引发Th 1应答又能在啮齿动物模型中起保护作用的药物。已经开发了几种动物模型来评价疫苗效力，目前正在用于进一步表征候选疫苗和佐剂/递送系统。我们建议使用最先进的免疫学检测方法，通过在临床和地理上不同的人群中进行广泛的检测，扩大候选疫苗抗原的评价。本节将提供关于不同分离株感染的遗传多样性人群中抗原保守性的重要信息。这些研究还将为确定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制剂进行免疫原性研究。我们还将对AS 02 A中Mtb 72 f免疫的人类志愿者的免疫应答进行详细分析，AS 02 A是第一个进入临床试验的确定的结核病疫苗。最后，我们将在啮齿动物感染和疾病模型中测试抗原/疫苗制剂。到资助期结束时，我们将确定进入临床试验的第二种候选疫苗。

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.