COCCIDIOIDES IMMITIS ANTIGENS AS VACCINES

犬球孢子菌抗原作为疫苗

• 批准号: 6347212
• 负责人: Theo N Kirkland
• 金额: $ 15.71万
• 依托单位: VETERANS MEDICAL RESEARCH FDN/SAN DIEGO
• 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 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6347212
• 关键词: Coccidioides immitis; T lymphocyte; cellular immunity; clinical research; coccidioidomycosis; disease /disorder model; fungal antigens; fungal proteins; fungal vaccines; human tissue; laboratory mouse; leukocyte activation /transformation; lymphokines; recombinant proteins; tissue /cell culture; vaccine development; vector vaccine

The overall goal of this program is to define C. immitis antigens which are effective vaccines in experimental coccidioidomycosis, and presumably, hman coccidioidomycosis. Since T- cell mediated immunity is critical in coccidioidomycosis, we propose to test antigens which elicit vigorous T- cell responses. The role of this project is essentially twofold: to perform the immunologic testing in mice, selecting candidate antigens for immunoprotection experiments; and to test those antigens as vaccines in mice. We will use a two-pronged approach to find T-cell reactive C. immitis antigens. We have already identified and cloned one protein which stimulated a C. immitis-specific murine T-cell line, as well as the C. immitis homologs of two heat-shock proteins, hsp 60 and dnaJ. These will be tested for ability to stimulate T-cell proliferation in lymph node T- cells from immune mice and several spherule-specific T-cell lines. These will also be tested for their ability to immunize mice for a proliferative response to C. immitis spherules. In collaboration with Project 3, we will determine what type of T-cells are activated by these antigens and what lymphokines they produce. A second, complementary approach will be to test cDNA libraries derived from spherules for T-cell reactivity. The clones expressing C. immitis proteins will be expressed in "naked vectors" and the mice "infected" with the DNA. The T-cell proliferative responses of the mice will be determined, and those that elicit T-cell responses will be expressed as recombinant proteins and tested as outlined above. The magnitude of the T-cell responses, the ability to elicit good responses against intact spherules, and the lymphokines produced will be factors in deciding which antigens will be tested for immunoprotection. Immunoprotection assays will be done in two strains of genetically susceptible mice. Single proteins will be tested first and then combinations. We anticipate that these studies will provide information critical to the development of a human vaccine.

这个项目的总体目标是确定免疫假丝酵母抗原