A novel vaccine for Aspergillus fumigatus

描述(申请人提供)：烟曲霉是一种无处不在的带孢子的真菌，可导致人类多种疾病。这些疾病包括过敏性肺哮喘、曲菌球和侵袭性疾病，这些疾病通常具有潜在的诱因。例如，1996年在美国，估计有10,190人因曲霉病住院；这导致1970人死亡，176,300天住院，以及6.331亿美元的费用。平均住院时间为17.3天，费用约为6.2万美元。尽管与曲霉病相关的住院治疗只占美国住院患者的一小部分，但这种情况下住院的患者住院时间长，死亡率高。死亡率高(在某些情况下超过90%)的部分原因是缺乏快速和灵敏的诊断测试(诊断往往是在死后进行的)，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烟曲霉菌疫苗。在这个SBIR第一阶段的提案中，我们将使用一种新型的、专有的重组抗原递送系统，并测试一些烟曲霉菌蛋白作为疫苗候选。我们将通过两个具体目标来实现这一目标： 具体目的一：利用重组DNA技术，使酵母细胞分别表达七种可能的烟曲霉菌抗原。 具体目标二：测试每种疫苗配方的体内效力，以保护接种的动物免受烟曲霉菌的攻击。 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、随后的第二阶段和第三阶段的研究将导致针对烟曲霉的疫苗的开发。

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.