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（由申请方提供）：球孢子菌病，也称为圣华金河谷热，是一种由粗球孢子菌引起的真菌疾病，在亚利桑那州南部、加州中部、新墨西哥州南部和德克萨斯州西部部分地区流行。 不仅永久居民，而且农业工人迁移到这些地区增加了对C的暴露。在土壤中处于休眠状态的犬疫霉孢子，当土壤被翻动时，孢子通过空气传播并被吸入。 一旦进入肺部，节孢子就会变成小球体。 急性呼吸道感染发生在接触后七天到三周之间，通常很快就会消退。 然而，在相当数量的情况下，慢性肺部疾病或传播到脑膜，骨骼和关节可能导致急性，危及生命的疾病。 接触C的流动劳工。传染病是一个高度移动的和代表性不足的人口，不幸的是，这种疾病在很大程度上没有得到医学界的承认。 已经使用了多种方法来对抗球孢子菌病，包括土壤处理，但只有疫苗才能完全消除这种“新兴疾病”。" 目前，有许多C。使用多种方法包括选择的重组表达抗原的免疫疫苗努力。 我们的长期目标是开发一种安全有效的抗C.伊米蒂斯。 在SBIR第一阶段的提案中，我们将与Garry T博士合作。科尔，约翰Galgiani博士，大卫A. Stevens和R.杜克公司，并使用Globelmmune的新型专利重组酵母输送系统，测试表达C.作为疫苗候选物的免疫炎蛋白。 我们将通过两个具体目标实现这一目标： 目的一：工程化酵母细胞表达三种C.利用重组DNA技术制备犬免疫球蛋白抗原。 目的二：检测每种疫苗制剂保护接种动物抵抗C.伊米蒂斯。 这项工作将是第二阶段工作的前奏，第二阶段工作将包括在几个C. immitis感染模型。 最终，I期和随后的II/III期研究将导致针对C的疫苗的开发。伊米蒂斯。