A novel vaccine for Aspergillus fumigatus

描述（由申请人提供）：烟曲霉是一种普遍存在的携带孢子的真菌，可引起人类多种疾病。这些包括过敏性肺哮喘、曲菌瘤和宿主的侵袭性疾病，通常伴有诱发性基础疾病。例如，1996年在美国，估计有10，190例曲霉病相关住院;这些导致1970例死亡，176，300个住院日和6.331亿美元的费用。平均住院时间为17.3天，费用约为62 000美元。虽然曲霉菌病相关的住院治疗占美国住院治疗的一小部分，但因该病住院的患者住院时间长，死亡率高。高死亡率（在某些情况下超过90%）的部分原因是缺乏快速和敏感的诊断测试（诊断通常是在死后进行的）以及缺乏有效的抗真菌药物。 我们的长期目标是开发一种安全有效的抗A.烟熏。在SBIR第一阶段的建议中，我们将使用一种新的、专有的重组抗原递送系统，并测试一些A。 烟曲霉蛋白作为疫苗候选物。 我们将通过两个具体目标实现这一目标： 具体目标一：工程酵母细胞表达七个A。烟曲霉推定抗原的重组DNA技术。 具体目标二：检测每种疫苗制剂保护接种动物免受A.烟熏。 这项工作将是第二阶段工作的前奏，第二阶段工作将包括对每种候选疫苗的体内功效和安全性的详细测试。最终，第一阶段，随后的第二阶段和第三阶段研究将导致针对A的疫苗的开发。烟熏。

DESCRIPTION (provided by applicant): Aspergillus fumigatus is a ubiqutous spore-bearing fungus that causes multiple diseases in humans. These include allergic pulmonary asthma, aspergillomas, and invasive disease of hosts usually with predisposing underlying conditions. For example, in the United States in 1996, there were an estimated 10,190 aspergillosis-related hospitalizations; these resulted in 1970 deaths, 176,300 hospital days, and $633.1 million in costs. The average hospitalization lasted 17.3 days at a cost of about $62,000. Although aspergillosis-related hospitalizations account for a small percentage of hospitalizations in the United States, patients hospitalized with the condition have lengthy hospital stays and high mortality rates. The high mortality rates (in some instances over 90%) are due in part to the lack of rapid and sensitive diagnostics tests (all too often the diagnosis is done post mortem) as well as the lack of effective anti-fungals. Our long-term goal is to develop a safe and effective vaccine against A. fumigatus. In this SBIR Phase I proposal, we will use a novel, proprietary recombinant antigen delivery system and test a number of A. fumigatus proteins as vaccine candidates. We will accomplish this in two specific aims: Specific Aim One: Engineer yeast cells to express each of seven A. fumigatus putative antigens using recombinant DNA technology. Specific Aim Two: Test the in vivo efficacy of each vaccine formulation to protect vaccinated animals against a challenge of A. fumigatus. 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, subsequent Phase II and III research will lead to the development of a vaccine against A. fumigatus.