Rapid point-of-care test for hepatitis C virus (HCV) core antigen to screen active HCV infection

丙型肝炎病毒 (HCV) 核心抗原的快速护理点检测，以筛查活动性 HCV 感染

• 批准号: 10254771
• 负责人: Tian Lan
• 金额: $ 22.4万
• 依托单位: GLUCOSENTIENT, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10254771
• 关键词: Adult; Amino Acids; Anti-Retroviral Agents; Antibodies; Antigens; Area; Biological; Biological Assay; Blood Glucose; Blood specimen; Buffers; Cause of Death; Centers for Disease Control and Prevention (U.S.); Cessation of life; Chronic; Chronic Hepatitis C; Cirrhosis; Clinical; Clinical Research; Contracts; Custom; Developing Countries; Development; Device or Instrument Development; Diagnosis; Disease; Early Intervention; Epidemic; Glucose; Goals; HCV screening; Healthcare; Hepatitis B Virus; Hepatitis C; Hepatitis C Antibodies; Hepatitis C Prevalence; Hepatitis C Vaccine; Hepatitis C virus; Human Resources; Immunoassay; Improve Access; Individual; Infection; Infrastructure; Intervention; Laboratories; Lead; Life; Liver diseases; Maintenance; Malignant Neoplasms; Measures; Medical; Microfluidics; Molecular Diagnostic Testing; Nucleic Acid Amplification Tests; Nucleic Acids; Performance; Pharmaceutical Preparations; Phase; Point-of-Care Systems; Population; Price; Procedures; Process; Production; Quality of life; Rapid screening; Renal function; Risk; Sampling; Societies; Step Tests; System; Technology; Testing; Time; Training; United States; Validation; Viral; Viral Antigens; Virus; acute infection; antibody test; antigen test; antiretroviral therapy; assay development; base; chronic infection; cost; curative treatments; design; detection limit; detection platform; effective therapy; follow-up; glucose monitor; healing; high risk; improved; infection rate; large scale production; liver injury; meter; operation; point of care; point of care testing; prototype; research and development; scale up; screening; success; vaccine access; viral DNA; virus core; young adult

Project Summary / Abstract The number of people testing positive for hepatitis C virus (HCV) has increased significantly in the last decade and younger adults contracting the virus has become more common. Now, roughly 50,000 infections are expected each year and about 40% of the people are not aware of their infections. Although, about half of these acute infections can be cleared by the individual, the remainder will become chronically infected. If hepatitis C is undiagnosed and remains untreated, severe liver damage and death can occur. HCV related liver damage is now a leading cause of death in the U.S., claiming ~15,000 lives annually. Although no vaccine for HCV is currently available, effective anti-retroviral treatment does exist to treat the disease with over 95% cure rate. Hence, identifying people with hepatitis C (chronic infection) is a critical task to treat and stop the spread of HCV. Currently, screening and diagnosing active HCV infection requires two tests. One antibody test to determine prior exposure and one nucleic acid test (NAT) to confirm an active infection. However, this two-step procedure is cumbersome and heavily relies on clinical laboratories; additionally, the antibody is not sensitive in the first two months of a new HCV infection and missing these cases. Hence, the current testing procedure has become the bottleneck for screening hepatitis C. Besides the current two-step approach, HCV core antigen (cAg) test has been proposed as an equally effective approach for screening and diagnosing active HCV infections. Numerous clinical studies since the 2000s have demonstrated a highly sensitive cAg test can be used to screen active HCV infection as effectively as NAT. However, all currently available HCV cAg test can only be performed in a laboratory setting and require trained personnel for operation and maintenance. As a result, this Phase I project is proposed to demonstrate the feasibility of developing a highly sensitive cAg test that can be performed quickly and accurately at the point-of- care (POC) by utilizing a detection platform based on the existing Blood Glucose Meter (BGM) hardware and a disposable microfluidic assay cartridge. Today’s BGM is the culmination of decades of R&D, designed for small footprint, simple operation, low cost and large-scale production. Leveraging the BGM technology with a familiar assay format for new applications allows us to reduce the risk and costs associated with device development and scale-up production. The final product will be a POC system composed of a BGM based meter and disposable cartridges for HCV cAg for measuring cAg levels in high risk individuals. The new POC HCV cAg test will be able to quickly identify individuals with chronic HCV infection and allow early curative treatment. The proposed product will also greatly benefit developing countries with high HCV prevalence but lacking testing infrastructure. The project will include three development goals, including 1) develop and optimize a highly sensitive cAg test using the BGM platform; 2) validate the BGM based cAg test in biological samples; and 3) integrating the optimized assay with an existing prototype system.

项目概要/摘要 过去十年中，丙型肝炎病毒 (HCV) 检测呈阳性的人数显着增加 年轻人感染病毒已变得更加普遍。现在，大约有 50,000 例感染 每年都有大约 40% 的人不知道自己受到感染。虽然，其中大约有一半 急性感染可以被个体清除，其余的将变成慢性感染。如果丙型肝炎是 未经诊断和治疗，可能会发生严重的肝损伤和死亡。 HCV 相关的肝损伤是 现在是美国的主要死亡原因，每年夺去约 15,000 人的生命。虽然目前还没有针对 HCV 的疫苗 目前，确实存在有效的抗逆转录病毒治疗方法，治愈率超过95%。 因此，识别丙型肝炎（慢性感染）患者是治疗和阻止丙型肝炎病毒传播的一项关键任务。 目前，筛查和诊断活动性丙型肝炎病毒感染需要两项测试。一项抗体测试即可确定 之前的暴露和一次核酸检测（NAT）以确认活动性感染。然而，这个两步程序 繁琐且严重依赖临床实验室；此外，该抗体在第一阶段不敏感 两个月后出现新的丙型肝炎病毒感染，但漏掉了这些病例。因此，当前的测试程序已变为 丙型肝炎筛查的瓶颈。 除了目前的两步方法外，HCV 核心抗原 (cAg) 检测也被认为是一种同样有效的方法。 筛查和诊断活动性 HCV 感染的方法。 2000年代以来的大量临床研究表明 证明高度敏感的 cAg 测试可与 NAT 一样有效地筛查活动性 HCV 感染。 然而，目前所有可用的 HCV cAg 检测只能在实验室环境中进行，并且需要经过培训 操作和维护人员。因此，建议该第一阶段项目展示 开发一种可在现场快速准确地进行的高灵敏度 cAg 测试的可行性 利用基于现有血糖仪 (BGM) 硬件和 一次性微流体检测盒。今天的 BGM 是数十年研发的结晶，专为小型音乐而设计 占地面积小、操作简单、成本低、可规模化生产。利用熟悉的 BGM 技术 新应用的检测格式使我们能够降低与设备开发相关的风险和成本 并扩大生产规模。最终产品将是一个 POC 系统，由基于 BGM 的仪表和 HCV cAg 一次性试剂盒，用于测量高危人群的 cAg 水平。新的 POC HCV cAg 检测 将能够快速识别慢性丙型肝炎病毒感染者并进行早期治疗。这 拟议的产品还将大大有利于丙肝病毒流行率高但缺乏检测的发展中国家 基础设施。 该项目将包括三个开发目标，包括1）开发和优化高度敏感的cAg 使用BGM平台进行测试； 2) 验证生物样本中基于 BGM 的 cAg 测试； 3）整合 使用现有原型系统优化测定。