HUMAN T CELLS ANTIGENS OF MYCOBACTERIUM TUBERCULOSIS

描述(改编自申请人的摘要)：本提案旨在 结核分枝杆菌T细胞抗原的鉴定和鉴定 重要的候选疫苗。鉴定新的结核分枝杆菌抗原，它们可能是 在对结核病的保护性免疫方面，我们使用了各种 抗原发现方法，强调用抗M。 结核抗血清和人类T细胞。8种候选疫苗(结核分枝杆菌8.4、结核分枝杆菌 9.8、Mtb 9.9、Mtb 11、Mtb 19、Mtb 32、Mtb 39、Mtb 40 基于他们刺激感染了M。 肺结核。这8个抗原基因将被评估为重组 抗原或作为裸DNA，单独或组合，用于免疫原性和 食蟹猴等三种动物模型对结核病的保护作用 猴子、老鼠和豚鼠。这些模型将用于评估T细胞 应对和保护。此外，我们还将强调使用 人T细胞表达克隆以鉴定其他疫苗候选抗原。 这些将在上述体外和动物模型中得到表征。

DESCRIPTION (Adapted from the Applicant's Abstract): This proposal is aimed at identifying and characterizing T cell antigens of M. tuberculosis which may be important vaccine candidates. To identify novel Mtb antigens which may be relevant in protective immunity against tuberculosis we have used a variety of antigen discovery methods which emphasize expression cloning with anti-M. tuberculosis antisera and human T cells. Eight vaccine candidates (Mtb 8.4, Mtb 9.8, Mtb 9.9, Mtb 11, Mtb 19, Mtb 32, Mtb 39, Mtb 40) have so far been selected based on their ability to stimulate PBMC from donors infected with M. tuberculosis. These eight antigen genes will be evaluated as recombinant antigens or as naked DNA, alone or in combination, for immunogenicity and protection against tuberculosis in three animal models including cynomolgus monkeys, mice, and guinea pigs. These models will be used to assess T cell responses as well as protection. In addition, we will emphasize the use of human T cell expression cloning to identify other vaccine candidate antigens. These will be characterized in the in vitro and animal models as above.