A novel yeast vaccine against Coccidioides Immitis

描述（由申请人提供）：球孢子菌病，也被称为圣华金谷热，是一种由球孢子虫引起的真菌疾病，在亚利桑那州南部、加利福尼亚州中部、新墨西哥州南部和德克萨斯州西部部分地区流行。迁移到这些地区的不仅是永久居民，还有农业工人，都增加了接触潜伏在土壤中的芽胞杆菌孢子的机会，随着土壤的转动，芽胞杆菌孢子通过空气传播并被人吸入。一旦进入肺部，关节孢子就变成小球体。急性呼吸道感染在接触后7天至3周内发生，通常会迅速消退。然而，在相当数量的病例中，可导致慢性肺部疾病或传播到脑膜、骨骼和关节，从而导致危及生命的急性疾病。暴露于C. imimitis的农民工是一个高度流动和代表性不足的人群，不幸的是，这种疾病在医学界基本上没有得到承认。人们已经使用了多种方法来对抗球孢子菌病，包括土壤治疗，但只有疫苗才能完全消除这种“新出现的疾病”。

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.