A novel yeast vaccine against Coccidioides Immitis

一种针对粗球孢子菌的新型酵母疫苗

• 批准号: 6645740
• 负责人: Claude P Selitrennikoff
• 金额: $ 10万
• 依托单位: MYCOLOGICS, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-06-15 至 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6645740
• 关键词: Coccidioides immitis; fungal proteins; fungal vaccines; gene delivery system; genetic manipulation; laboratory mouse; recombinant DNA; recombinant proteins; transfection /expression vector; vaccine development; vector vaccine; yeasts

DESCRIPTION (provided by applicant): Coccidioidomycosis, also known as San Joaquin Valley Fever, is a fungal disease caused by Coccidioides immitis that is endemic in portions of Southern Arizona, central California, southern New Mexico and west Texas. The migration of not only permanent residents, but also agricultural workers to these areas increases exposure to C. immitis spores that lie dormant in the soil, and as the soil is turned, the spores become airborne and are inhaled. Once in the lungs, the arthroconidia transform into spherules. An acute respiratory infection occurs between seven days to three weeks after exposure and often resolves rapidly. However, in a significant number of cases, chronic pulmonary conditions or dissemination to the meninges, bones, and joints can result, leading to acute, life-threatening disease. Migrant laborers who are exposed to C. immitis are a highly mobile and underrepresented population, and unfortunately, this disease goes largely unacknowledged in the medical community. A variety of approaches have been used to fight coccidioidomycosis, including soil treatments, but only a vaccine can completely eliminate this "emerging disease." Currently, there are a number of C. immitis vaccine efforts that use a variety of approaches including selected recombinantly-expressed antigens. Our long-term goal is to develop a safe and effective vaccine against C. immitis. In this SBIR Phase I proposal, we will collaborate with Dr. Garry T. Cole, Dr. John Galgiani, Dr. David A. Stevens, and Dr. R. Duke of Globelmmune, Inc., and use Globelmmune's novel, proprietary recombinant yeast delivery system and test heat-killed yeast cells expressing C. immitis proteins as vaccine candidates. We will accomplish this in two specific aims: Aim One: Engineer yeast cells to express three C. immitis antigens using recombinant DNA technology. Aim Two: Test the in vivo efficacy of each vaccine formulation to protect vaccinated animals against a challenge of C. immitis. This work will be a prelude to work in Phase II that will include detailed testing for in vivo efficacy and safety of each vaccine candidate in several C. immitis infection models. Ultimately, the Phase I and subsequent Phase II/III research will lead to the development of a vaccine against C. immitis.

描述（由申请人提供）：球虫菌病，也称为圣华金河谷发烧，是由球虫毒剂Immitis引起的一种真菌疾病，在亚利桑那州南部，加利福尼亚州中部，新墨西哥州和西德克萨斯州的部分地区是特有的。 不仅永久居民的迁移，而且农业工人到这些地区的迁移会增加暴露于处于土壤上休眠的孢子的孢子孢子虫，随着土壤的变形，孢子会变得空中流动并被吸入。 一旦进入肺部，节肢动物转变为球形。 急性呼吸感染发生在暴露后的7天到三周之间，并且经常迅速解决。 但是，在大量病例中，慢性肺部条件或向脑膜，骨骼和关节传播可能会导致急性，威胁生命的疾病。 暴露于C. Immitis的移民劳动者是一个高度流动性和代表性不足的人口，不幸的是，这种疾病在医学界基本上未被承认。 已经使用了多种方法来抵抗球虫菌病（包括土壤处理），但只有疫苗才能完全消除这种“新兴疾病”。 当前，有许多使用多种方法包括精选重组表达的抗原的方法。 我们的长期目标是开发针对侵入性疾病的安全有效疫苗。 在此SBIR第一阶段提案中，我们将与Garry T. Cole博士，John Galgiani博士，David A. Stevens博士和Globelmmune，Inc。的R. Duke博士合作，并使用Globelmmune的小说，专有的重组酵母菌递送系统和测试热杀死的酵母细胞表达C. immitic C. immitic Prote蛋白作为疫苗的捕获率cantatrates canticatates。 我们将以两个具体的目标来实现这一目标： 目标一：工程酵母细胞使用重组DNA技术表达三种抗原抗原。 目标二：测试每种疫苗配方的体内功效，以保护疫苗的动物免受炎症炎的挑战。 这项工作将是在第二阶段工作的前奏，其中包括在几种炎症性炎感染模型中对每个疫苗候选者的体内功效和安全性进行详细测试。 最终，第一阶段和随后的II/III期研究将导致针对Immisis的疫苗开发。