A novel recombinant vaccine against Cryptococcus.

描述(申请人提供)：新生隐球菌是一种被包裹的致病酵母菌，可引起人类和其他动物的肺部感染和脑膜脑炎。在过去的20年里，全世界隐球菌病的发病率急剧增加，这不仅反映了艾滋病毒感染的增加，也反映了免疫缺陷患者数量的增加。CD4+T细胞的丧失使患者容易受到新生梭菌的进行性感染--这强调了细胞介导的免疫在宿主抵抗中的作用。 我们的长期目标是发现治疗真菌疾病的新药，并开发针对多种人类致病真菌的疫苗。在这项第一阶段的STTR提案中，我们计划开发一种安全有效的新型弧菌疫苗。我们将使用一种新的抗原递送系统，并测试一些新生葡萄球菌蛋白作为候选疫苗。我们将通过两个具体目标来实现这一目标： 具体目标一：利用重组DNA技术使酵母细胞分别表达5种新生葡萄球菌蛋白。 具体目标二：测试每种疫苗配方的体内效力，以保护接种疫苗的动物免受新城疫杆菌的挑战。 这项工作将是第二阶段工作的前奏，该阶段将包括对每个候选疫苗的体内有效性和安全性进行详细测试。最终，第一阶段、第二阶段和第三阶段的研究将导致针对新生葡萄球菌的疫苗的开发

DESCRIPTION (provided by applicant): Cryptococcus neoformans is an encapsulated pathogenic yeast that causes pulmonary infections and meningoencephalitis in humans and other animals. During the last 20 years, there has been a dramatic increase in the incidence of cryptococcosis throughout the world that mirrors the increase in not only HIV infections, but also in the growing number of immuno compromised patients. Loss of CD4+ T cells predisposes patients to progressive infection with C. neoformans--this emphasizes the role of cell mediated immunity in host resistance. Our long-term corporate goals are to discover new drugs for the treatment of fungal diseases and to develop vaccines against a number of human pathogenic fungi. In this Phase I STTR proposal, we plan to develop a safe and effective vaccine against C. neoformans. We will use a novel antigen delivery system and test a number of C. neoformans proteins as vaccine candidates. We will accomplish this in two specific aims: Specific Aim One: Engineer yeast cells to express each of five C. neoformans proteins using recombinant DNA technology. Specific Aim Two: Test the in vivo efficacy of each vaccine formulation to protect vaccinated animals against a challenge of C. neoformans. 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. Ultimately, the Phase I, Phase II and Phase lll research will lead to the development of a vaccine against C. neoformans