Detection of HIV proteins in urine to diagnose infection

检测尿液中的 HIV 蛋白以诊断感染

• 批准号: 9908301
• 负责人: James W Lillard
• 金额: $ 29.62万
• 依托单位: NEWMARK DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-12 至 2021-09-11
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9908301
• 关键词: Accident and Emergency department; Acute; Agreement; Antibodies; Area; Benchmarking; Biological Assay; Blood Banks; Blood specimen; Clinic; Country; Data; Detection; Development; Development Plans; Devices; Diagnosis; Diagnostic; Diagnostic tests; Disease; Doctor of Philosophy; Environment; Enzyme Immunoassay; Evaluation; FDA approved; Foundations; Future; Goals; Government; HIV; HIV Infections; HIV serology; Health; Home environment; Human immunodeficiency virus test; Individual; Industry; Infection; Infrastructure; Institution; Intellectual Property; Lateral; Legal patent; Licensing; Measures; Medical; Methods; Monitor; Morehouse School of Medicine; Patients; Performance; Phase; Physicians' Offices; Plasma; Pregnancy Tests; Privatization; Proteins; Reader; Receiver Operating Characteristics; Research; Resources; Sampling; Sensitivity and Specificity; Serologic tests; Small Business Technology Transfer Research; Statistical Data Interpretation; Technology; Testing; Time; Urine; Vaccination; Viral Load result; Viral Proteins; Viral load measurement; antiretroviral therapy; base; cost; design; diagnostic assay; exosome; extracellular vesicles; novel; off-patent; point-of-care diagnostics; product development; programs; research study; standard of care; urinary; volunteer

PROJECT SUMMARY/ABSTRACT The development of a low cost, point of care diagnostic device or kit in a “rapid test” or “self test” format would be highly beneficial to the global effort to diagnose, manage and treat HIV. We are proposing to evaluate the scientific finding that HIV proteins are present in urine associated with extracellular vesicles, also commonly referred to as exosomes. The development of one or more diagnostic tests designed to detect and measure extracellular vesicle-associated HIV proteins in urine is the ultimate goal. Because viral proteins are detected, and not HIV-specific antibodies, this type of diagnostic assay will be useful for detecting infection, including during the acute phase prior to the development of antibodies, monitoring disease status under antiretroviral therapy and discriminating between infection and vaccination. Products can be developed and ultimately produced using technologies and materials that are standard to the industry and assay formats can be produced as standard EIA kits or as single patient lateral flow devices, similar to home pregnancy tests. Preliminary data are limited but they clearly demonstrate that HIV proteins can be readily detected in the urine of HIV patients. The findings are novel, patent protected in all major potential markets and manufacturing countries. The intellectual property is available to NewMark Diagnostics LLC through an exclusive option license agreement. For the proposed research we will critically evaluate the working hypothesis that viral load in HIV+ patients, measured in plasma, is positively correlated with our ability to detect extracellular vesicle-associated HIV proteins in urine. To accomplish this, we will first determine the plasma viral load using blood samples provided by HIV+ volunteers using an FDA-approved PCR-based test. A research level extracellular vesicle capture EIA will then be used to measure the concentration of multiple HIV proteins in urine samples obtained from the same HIV+ volunteers. We will determine preliminary “assay cut-off values” as an estimate of the EIA sensitivity using multiple statistical analyses including Receiver Operator Characteristic Curves. The evaluation of the basic scientific discovery in this manner is a crucial first step towards the potential future development of a new type of rapid diagnostic test for HIV that can be used globally and in numerous settings.

项目概要/摘要 以“快速测试”或“自检”形式开发低成本的护理点诊断设备或套件将 对全球诊断、管理和治疗艾滋病毒的努力非常有益，我们建议对艾滋病毒进行评估。 科学发现，尿液中存在与细胞外囊泡相关的 HIV 蛋白，也常见 被称为外泌体的一种或多种诊断测试的开发，旨在检测和测量。 尿液中细胞外囊泡相关的 HIV 蛋白是最终目标，因为检测到病毒蛋白， 而不是 HIV 特异性抗体，这种类型的诊断测定将有助于检测感染，包括 在抗体产生之前的急性期，在抗逆转录病毒治疗下监测疾病状况 最终可以开发出治疗方法以及区分感染和疫苗接种的产品。 使用行业标准的技术和材料生产，并且检测格式可以 作为标准 EIA 套件或单个患者侧流装置生产，类似于家庭妊娠测试。 初步数据有限，但它们清楚地表明可以在尿液中轻松检测到 HIV 蛋白 该研究结果是新颖的，在所有主要潜在市场和制造领域均受到专利保护。 NewMark Diagnostics LLC 通过独家选择权可获得该知识产权。 许可协议。 对于拟议的研究，我们将严格评估 HIV+ 患者中病毒载量的工作假设， 在血浆中测量，与我们检测细胞外囊泡相关 HIV 的能力呈正相关 为了实现这一目标，我们首先使用血液样本测定血浆病毒载量。 由 HIV+ 志愿者使用 FDA 批准的基于 PCR 的 A 研究级细胞外囊泡测试提供。 capture EIA 随后将用于测量获得的尿液样本中多种 HIV 蛋白的浓度 我们将确定初步的“检测截止值”作为 EIA 的估计值。 使用多种统计分析（包括接收者操作员特征曲线）来确定灵敏度。 以这种方式评估基础科学发现是迈向潜在未来的关键的第一步 开发一种新型艾滋病毒快速诊断测试，可在全球和许多环境中使用。