Immunoassay for diagnosis of invasive fungal disease

描述（由申请人提供）：感染性疾病的早期诊断对患者结局至关重要。一个重要的早期问题是-“它是真菌，细菌还是病毒？“一个快速的 这个问题的答案将允许先发制人的治疗，可以挽救生命。该项目的目标是一种快速廉价的免疫测定法，将使用血清作为样本，以广泛识别侵袭性真菌病（IFD）的存在。这是真菌感染诊断的一个未满足的需求，特别是对于患者护理点附近的测试。目标人群将是先进的医疗干预和使用强效免疫抑制药物导致机会性和地方性真菌感染扩散的个体。总的假设是，选定的多糖和蛋白质抗原是由病原真菌产生的，这些病原真菌在产生侵袭性疾病的属中是共有的。此外，这些抗原的子集以允许检测的浓度流入血液。该方法将是针对两种不同抗原的存在的免疫测定，所述两种不同抗原i）在引起IFD的真菌物种中共有，和ii）在感染期间流入血液。同时检测两种不同的抗原将显着提高预测值。将使用侧流免疫测定（LFA）和/或酶联免疫测定（ELISA）平台对产品进行检测。在该I期STTR中成功的标准是产生与两种不同的真菌抗原反应的mAb，一种是多糖，另一种是蛋白质，这是IFD的主要原因所共有的。靶向两种独立的抗原将产生具有高预测值的测定。如果该第一阶段项目成功，第二阶段应用将以LFA或ELISA形式构建免疫测定，并进行临床前验证，以广泛诊断侵袭性真菌疾病。如果成功，这项转化研究项目可以通过早期诊断和治疗降低侵袭性真菌病的死亡率。

DESCRIPTION (provided by applicant): Early diagnosis of infectious disease is critical to patient outcome. An important early question is - "is it a fungus, a bacterium or a virus?" A rapid answer to this question would allow preemptive treatment that can save lives. The goal of this project is a rapid and inexpensive immunoassay that will use serum as a sample to broadly identify the presence of invasive fungal disease (IFD). This is an unmet need for diagnosis of fungal infection, particularly for tests near the point of patient care. The target population willbe individuals for whom advanced medical intervention and use of potent immunosuppressive drugs has led to a proliferation of opportunistic and endemic fungal infection. The overall hypothesis is that selected polysaccharide and protein antigens are produced by pathogenic fungi that are shared across the genera that produce invasive disease. Moreover, a subset of these antigens is shed into blood in concentrations that would allow for detection. The approach will be immunoassay for the presence of two distinct antigens that i) are shared across fungal species that cause IFD and ii) are shed into blood during infection. Simultaneous detection of two distinct antigens will markedly enhance the predictive value. The product will be assays with the lateral flow immunoassay (LFA) and/or enzyme-linked immunoassay (ELISA) platforms. Criteria for success in this Phase I STTR would be production of mAbs reactive with two distinct fungal antigens, one a polysaccharide and the other a protein, that are shared by the major causes of IFD. Targeting of two independent antigens will produce an assay with a high predictive value. If this Phase I project is successful, a Phase II application would construct immunoassays in LFA or ELISA format and perform pre- clinical validation for broad diagnosis of invasive fungal disease. If successful, this translational research project could reduce mortality due to invasive fungal disease through earlier diagnosis and treatment.