Immunoassay for diagnosis of invasive fungal disease

描述(由申请人提供)：传染病的早期诊断对患者的预后至关重要。一个重要的早期问题是--“它是真菌、细菌还是病毒？”一次快速的 对这个问题的回答将允许先发制人的治疗，从而拯救生命。这个项目的目标是一种快速和廉价的免疫分析方法，它将使用血清作为样本来广泛地识别侵袭性真菌病(IFD)的存在。对于真菌感染的诊断，这是一种未得到满足的需求，尤其是在患者护理点附近的测试中。目标人群将是先进的医疗干预和强有力的免疫抑制药物的使用导致机会性和地方性真菌感染扩散的个人。总体假设是，选定的多糖和蛋白质抗原是由致病真菌产生的，这些真菌在产生侵袭性疾病的属中共享。此外，这些抗原的一个子集被注入血液中，其浓度可以被检测到。该方法将通过免疫分析检测两种不同抗原的存在，这两种不同的抗原i)在引起IFD的真菌物种中共享，ii)在感染期间流入血液。同时检测两种不同的抗原将显著提高预测价值。该产品将通过侧向流动免疫分析(LFA)和/或酶联免疫分析(ELISA)平台进行检测。这一阶段STTR成功的标准将是产生与两种不同真菌抗原反应的单抗，一种是多糖，另一种是蛋白质，这两种抗原是引起IFD的主要原因。靶向两个独立的抗原将产生一种具有很高预测价值的检测方法。如果这个第一阶段的项目成功，第二阶段的应用程序将构建LFA或ELISA格式的免疫分析，并对侵袭性真菌疾病的广泛诊断进行临床前验证。如果成功，这项转化研究项目可能会通过更早的诊断和治疗来降低侵袭性真菌疾病的死亡率。

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.