Antigen Immunoassay for Diagnosis of Coccidioidomycosis

描述(申请人提供)：球孢子菌病，也被称为“谷热”，是一种由球孢子菌引起的真菌疾病。据估计，美国每年有15万人感染这种病毒。目前球孢子菌病的诊断依赖于患者血清中抗球虫抗体的检测。然而，在疾病的最初几周，这种血清学检测的敏感性特别低。改善早期诊断的有希望的策略 球虫感染的研究是从球虫中检测特定的蛋白抗原，这些抗原被排入尿液或血清中。然而，目前还没有基于抗原尿/抗原血症的球孢子菌病诊断方法，因此迫切需要开发这种类型的诊断方法。这个项目的目标是一种免疫分析，它将使用血清或尿液作为样本来诊断球孢子菌病。我们的总体假设是，蛋白质生物标记物靶标被释放到感染球虫的小鼠的尿液或血清中。该方法将利用单链抗体噬菌体展示技术来促进从感染球虫的小鼠的尿液和血清中识别球虫生物标记物。该产品将是横向流动分析(LFA)或酶免疫分析(EIA)格式的免疫分析，以促进球孢子菌病的早期诊断。这一阶段SBIR成功的标准将是从感染球虫的小鼠的尿液或血清中识别和验证至少一个蛋白质生物标记物。如果第一阶段项目的目标实现，第二阶段应用程序将使用第一阶段项目产生的蛋白质生物标记物(S)和/或抗体(S)来构建和评估LFA或EIA格式的免疫分析。如果成功，这一转化研究项目可以通过早期诊断大大降低与球孢子菌病相关的发病率和医疗费用。

DESCRIPTION (provided by applicant): Coccidioidomycosis, also known as "Valley Fever," is a fungal disease caused by Coccidioides spp. that infects an estimated 150,000 people each year in the United States. Current diagnosis of coccidioidomycosis relies on detection of anti-coccidioidal antibodies in patient sera. However, the sensitivity of this serological assay is particularly low in the first few weeks of illness. A promising strategy to improve early diagnosis of Coccidioides infections is to detect specific protein antigens from Coccidioides which are shed into urine or serum. However, antigenuria/antigenemia-based diagnostic assays for coccidioidomycosis are not yet available, resulting in a critical need for the development of this type of diagnostic. The goal of this project is an immunoassay that will use serum or urine as a sample to diagnose coccidioidomycosis. Our overall hypothesis is that protein biomarker targets are shed into the urine or serum of Coccidioides-infected mice. The approach will be the use of scFv phage display technology to facilitate the identification of Coccidioides biomarkers in urine and serum from Coccidioides-infected mice. The product will be an immunoassay in the lateral flow assay (LFA) or enzyme immunoassay (EIA) format in order to facilitate earlier diagnosis of coccidioidomycosis. Criteria for success of this Phase I SBIR would be the identification and validation of at least one protein biomarker from the urine or serum of Coccidioides-infected mice. If the goals of this Phase I project are achieved, a Phase II application will use the protei biomarker(s) and/or antibody(s) generated from this Phase I project to construct and evaluate an immunoassay in LFA or EIA format. If successful, this translational research project could dramatically decrease the morbidity and health care costs associated with coccidioidomycosis through earlier diagnosis.