Development of Coccidioides Cytokine Release Assay

球孢子菌细胞因子释放测定的发展

• 批准号: 10361440
• 负责人: Lawrence JOSEPH WHEAT
• 金额: $ 29.77万
• 依托单位: MIRAVISTA DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10361440
• 关键词: Acute; Acute Pneumonia; Algorithms; Antibodies; Antibody Response; Antifungal Therapy; Antigens; Area; Arizona; Biological Assay; Cellular Immunity; Characteristics; Clinical; Coccidioides; Coccidioides immitis; Coccidioides posadasii; Coccidioidomycosis; Collaborations; Cytomegalovirus; Data; Delayed Hypersensitivity; Detection; Development; Diagnosis; Diagnostic; Diagnostic tests; Disease; Early Diagnosis; Engineering; Enzyme-Linked Immunosorbent Assay; Epidemiology; Epitopes; Evaluation; FDA approved; Future; Geographic Locations; Goals; Grant; Health Care Costs; Human; Hypersensitivity skin testing; Immune; Immune response; Immunocompromised Host; Immunosuppression; Incidence; Individual; Infection; Interferon Type II; Interferons; Life; MHC Class I Genes; Marketing; Measurement; Measures; Methodology; Methods; Morbidity - disease rate; Mycobacterium tuberculosis; North America; Occupations; Organ Transplantation; Outcome; Patient Care; Patients; Performance; Persons; Phase; Pilot Projects; Pneumonia; Population; Preparation; Prevalence; Preventive; Production; Proteins; Public Health; Reaction; Reagent; Recombinants; Risk; Sampling; Scientist; Screening procedure; Serology; Serology test; Serum; Small Business Innovation Research Grant; Solid; Source; South America; Specificity; Standardization; Stratification; Stress; System; T cell response; Technology; Testing; Therapeutic immunosuppression; Time; Transgenic Mice; Travel; Tube; Tuberculosis; United States; Universities; Whole Blood; Wild Type Mouse; base; care costs; climate change; clinical care; cohort; community acquired pneumonia; cost; cytokine; desert fever; fungus; geographic population; high risk; immunological status; immunosuppressed; improved; latent infection; mortality; pathogen; predictive modeling; prognostic; prognostic value; response; risk stratification; scale up; screening panel; synthetic polymer Bioplex; tool; vaccine trial

Coccidioidomycosis (CM) is an endemic mycosis caused by the fungi Coccidioides immitis and Coccidioides posadasii, which is native to arid regions of North and South America. It is estimated that up to 350,000 infections occur annually in the U.S. Additionally, up to a third of community acquired pneumonia cases in these areas are thought to be a result of CM. Morbidity associated with CM is substantial with a median illness duration of 120 days. The costs associated with CM are high, with an estimated annual direct healthcare cost of nearly $200 million. Currently, the diagnosis of CM is primarily based on detection of anti-Coccidioides antibodies. Once infection clears, the antibody eventually becomes undetectable making it difficult to determine if there was previous exposure. Classically, delayed-type hypersensitivity reactions using skin tests have been used to evaluate the cellular immune response, which is indicative of past infection. The commercially available Coccidioides skin test has suboptimal performance characteristics and is not utilized often in clinical care. The use of an ex vivo cytokine release assay (CRA) avoids the limitations associated with skin testing while allowing for the detection of cytokines produced by stimulation with a pathogen- specific antigen. Analogous to the commercially available CRA for tuberculosis, a Coccidioides CRA would be a major advance for patient care and for evaluation of CM prevalence within geographical regions and populations. Our data suggests a CRA for CM will be valuable as a tool to detect patients with acute CM and stratify those with latent CM (those at risk for reactivation if immunosuppressed). Climate change and incidence modelling predict endemicity to expand from 12 to 18 states and incidence to increase by 50%, stressing the need for a public health screening tool to establish changing boundaries and stratification for high risk occupations and future vaccine trials., The goal of this application is to develop a test to assist in the diagnosis, management, and epidemiology of CM, which increasingly afflicts people living in or travelling through areas where it is endemic. This phase 1 grant will utilize technological advances and prediction modeling to produce recombinant antigens with the highest likelihood of stimulating a cellular immune response. These antigens will then be used to develop an in-tube CRA, the first of its kind to assist in the management of a fungal disease.

球孢子菌病(Coccidioidmycosis，CM)是一种由球孢子菌引起的地方性真菌病。 Posadasii球藻，原产于北美和南美洲的干旱地区。它是 据估计，美国每年发生多达35万例感染病例。此外，多达三分之一的 这些地区的社区获得性肺炎病例被认为是由CM引起的。 与CM相关的发病率很高，中位病程为120天。这个 与CM相关的成本很高，估计每年的直接医疗成本接近 2亿美元。 目前，CM的诊断主要基于抗球虫抗体的检测。 一旦感染清除，抗体最终就会变得无法检测，从而很难 确定以前是否接触过病毒。传统上，迟发性超敏反应 使用皮肤测试已经被用来评估细胞免疫反应，这表明 过去的感染。市面上可买到的球虫皮试性能不佳。 在临床护理中并不经常使用。 体外细胞因子释放试验(CRA)的使用避免了与皮肤相关的限制 在允许检测病原体刺激产生的细胞因子的同时进行测试- 特定的抗原。类似于商业上可获得的治疗结核病的CRA，球虫 CRA将是患者护理和评估CM患病率方面的重大进步 地理区域和人口。我们的数据表明，CM的CRA将作为 检测急性心肌梗死患者并对潜伏期心肌梗死患者(有发病风险的患者)分层的工具 如果免疫抑制，则重新激活)。气候变化和发病模型预测地方性 从12个州扩大到18个州，发病率增加50%，强调有必要 为高风险建立不断变化的边界和分层的公共健康筛查工具 职业和未来的疫苗试验。 此应用程序的目标是开发一种测试，以帮助诊断、管理和 CM的流行病学，它日益困扰着生活在或旅行于以下地区的人 这是地方病。这笔第一阶段的赠款将利用技术进步和预测建模来 生产最有可能刺激细胞免疫的重组抗原 回应。然后这些抗原将被用来开发管内CRA，这是第一个用来 协助管理一种真菌疾病。