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.

项目总结/摘要 以“快速测试”或“自我测试”形式开发低成本的护理点诊断装置或试剂盒将 对全球诊断、管理和治疗艾滋病毒的努力极为有益。我们建议评估 科学发现，HIV蛋白存在于尿液中，与细胞外囊泡相关，也通常 称为外泌体。一种或多种诊断测试的开发，旨在检测和测量 尿中的细胞外囊泡相关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用于检测感染，包括 在产生抗体之前的急性期，监测抗逆转录病毒治疗的疾病状况 治疗和区分感染和疫苗接种。可以开发产品，最终 使用工业标准的技术和材料生产， 作为标准EIA试剂盒或单个患者侧流装置生产，类似于家庭妊娠试验。 初步的数据是有限的，但他们清楚地表明，艾滋病毒蛋白可以很容易地检测到尿液中 艾滋病患者。这些发现是新颖的，在所有主要的潜在市场和制造业中受到专利保护 国家NewMark Diagnostics LLC可通过独家选项获得知识产权 许可协议。 对于拟议的研究，我们将严格评估工作假设，即HIV+患者的病毒载量， 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 尿液中的蛋白质为了实现这一点，我们将首先确定血浆病毒载量使用血液样本 由HIV+志愿者使用FDA批准的基于PCR的测试提供。研究水平的细胞外囊泡 捕获EIA将用于测量尿液样本中多种HIV蛋白的浓度 来自同一批HIV阳性志愿者。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（包括受试者操作特征曲线）进行敏感性分析。的 以这种方式对基础科学发现进行评估，是迈向潜在未来的关键的第一步 开发一种新型的艾滋病毒快速诊断测试，可在全球和许多环境中使用。