VACCINE DEVELOPMENT IN TUBERCULOSIS

结核病疫苗的开发

• 批准号: 6764161
• 负责人: Antonio Campos-Neto
• 金额: $ 28.64万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2005-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6764161
• 关键词: Macaca fascicularis; Mycobacterium tuberculosis; T lymphocyte; active immunization; bacterial antigens; cellular immunity; clinical research; guinea pigs; human subject; laboratory mouse; leukocyte activation /transformation; molecular cloning; recombinant proteins; tuberculosis vaccines; vaccine development; vector vaccine

This proposal is designed to identify, characterize, and clone Mycobacterium tuberculosis genes encoding proteins associated with specific T cell responses of presumed protected humans and animals. Antigens associated with both CD4+ and/or CD8+ T cell responses are the target of this proposal. The recent identification, by our group, of a novel and protective antigen opens new possibilities for vaccine development. Two other antigens/gene have been cloned, expressed, and purified. They will be evaluated for their ability to elicit T cell responses from human PBMC, primarily from non-BCG immunized PPD+ healthy individuals. The recombinant antigens alone and in combination will also be evaluated as vaccine candidates in three animal protection models, including mice, guinea pigs, and cynomolgus monkeys, all of which will be challenged by aerosol or intratracheal routes. In addition to the evaluation of these antigens, we will characterize and clone other vaccine candidates using recently developed approaches for the direct identification of both CD4 and CD8 T cell antigens.

该建议旨在识别，表征和克隆的结核分枝杆菌基因，这些基因编码与假定受保护的人类和动物的特定T细胞反应相关的蛋白质。 与CD4+和/或CD8+ T细胞反应相关的抗原是该建议的目标。 我们小组的最新鉴定是一种新颖的保护性抗原为疫苗开发开辟了新的可能性。 另外两个抗原/基因已被克隆，表达和纯化。 他们将评估他们从人PBMC引起T细胞反应的能力，主要是从非BCG免疫PPD+健康个体中引起的。在三种动物保护模型中，单独的重组抗原和组合也将作为候选疫苗评估，包括小鼠，豚鼠和cynomolgus猴子，所有这些都将受到气溶胶或运动内路线的挑战。除了评估这些抗原外，我们还将使用最近开发的方法来表征和克隆其他疫苗候选者，以直接鉴定CD4和CD8 T细胞抗原。