An Ultrasensitive and Low-Cost p24 Antigen Test for the Early Detection of HIV

用于早期检测 HIV 的超灵敏且低成本的 p24 抗原测试

• 批准号: 10482574
• 负责人: SEASON S-S WONG
• 金额: $ 29.96万
• 依托单位: AI BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10482574
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Americas; Antibodies; Antibody Response; Antigens; Area; Binding; Biological Assay; Biological Sciences; Blood specimen; Capsid; Capsid Proteins; Catalysis; Characteristics; Chemistry; Clinic; Complex; Data; Decentralization; Detection; Developed Countries; Developing Countries; Devices; Diagnosis; Diagnostic; Early Diagnosis; Electrical Resistance; Epidemic; Evaluation; Eye; Generations; Goals; Growth; Guidelines; HIV; HIV Antibodies; HIV Infections; HIV diagnosis; HIV-1; Human immunodeficiency virus test; Hydrogen Peroxide; Immune response; Immunoassay; Individual; Infection; Infrastructure; Joints; Jordan; Label; Laboratories; Lead; Light; Liquid substance; Magnetism; Measurement; Methods; Microfluidics; Monitor; Monoclonal Antibodies; Nanotechnology; Nucleic Acid Amplification Tests; Nucleic Acids; Oxygen; Patient Care; Patients; Persons; Phase; Physicians; Plasma; Platinum; Point of Care Technology; Process; RNA; Reagent; Resistance; Resource-limited setting; Reverse Transcriptase Polymerase Chain Reaction; Sampling; Signal Transduction; Small Business Innovation Research Grant; Syringes; Technology; Telephone; Testing; Time; Training; United Nations; United States National Institutes of Health; Universities; Validation; Viral; Viral Load result; Viremia; Virion; Virus; Virus Diseases; Washington; Whole Blood; Work; acute infection; antibody detection; antigen test; antiretroviral therapy; base; cost; cost effective; design; digital; evaluation/testing; high risk population; instrument; nanoparticle; particle; point of care; point of care testing; professor; programs; self testing; seroconversion; tool; transmission process

PROJECT SUMMARY The goal of this NIH SBIR Phase I proposal is to develop a low-cost and rapid point-of-care (POC) p24 test for early detection of human immunodeficiency virus (HIV) infection. It will be appropriate for use at decentralized settings in developed and developing countries where the limitations of infrastructure and laboratory capability prohibit viral load-based nucleic acid testing. Our aim is to maintain the accuracy and sensitivity of traditional lab-based diagnostics while providing a device that a minimally trained person can operate, significantly increasing access to HIV diagnostics. The WHO guidelines recommend initiating antiretroviral therapy (ART) as early as possible once infected, and the Joint United Nations Programme on HIV and AIDS (UNAIDS) has called for global increases in HIV testing, treatment, and viral suppression. However, because a significant proportion of individuals are unaware of their infection, expanding testing capabilities has a high potential to reach previously untested high-risk populations. Current point-of-care devices that can detect HIV viremia directly are too expensive and require some level of specialized training to operate. Also, many POC technologies that have been approved are not sensitive enough to detect HIV during peak viremia and transmissibility in acute infection. Existing self-testing technologies only detect the host antibody response, which arises weeks after the initial infection. Therefore, practical and affordable POC test platforms that enable decentralized testing will be important for the federal “Ending the HIV Epidemic: A Plan for America” initiative. To this end, AI Biosciences proposes to develop a low-cost magnetic particle (MP) and nanoparticle based sandwich immunoassay that can be used for the early-detection of HIV-1 p24 capsid protein with a sensitivity near that of nucleic acid amplification approaches. This small device (~4x3x2 inches) performs MP-based p24 capture and concentration, followed by labeling with antibody-modified platinum nanoparticles (PtNPs). The PtNPs then interact with a hydrogen peroxide solution to create a signal that can be recorded with extremely high sensitivity using low-cost electronic components. We aim to optimize the chemistry and assay form factor during Phase I to make a 30-min sample- to-answer test that requires minimal training and hands-on time. We will work with Professor Chuan-Jian Zhong, a nanotechnology and catalysis expert at Binghamton University (BU), to characterize and synthesize the antibody modified MPs and PtNPs. AI Biosciences has also partnered with Professor Jeanne Jordan of George Washington University (GWU)to assist with device evaluation and testing. At the end of Phase I, we will bring our device and assay to her laboratory to perform a technology demonstration. We will train technicians to use our device and assay for validation. They will compare the results from our immunoassay to PCR and 5th generation immunoassays. If our approach for sensitive p24 detection is successful, we will use the same approach for HIV antibody detection.

项目摘要 该NIH SBIR I期建议的目的是开发低成本和快速的护理（POC）P24测试 人类免疫缺陷病毒（HIV）感染的早期检测。它适用于分散的 在发达国家和发展中国家的设置，基础设施和实验室能力的局限性 禁止基于病毒负荷的核酸测试。我们的目的是保持传统的准确性和敏感性 基于实验室的诊断，在提供最低训练的人可以操作的设备时， 增加获得HIV诊断的机会。 WHO指南建议启动抗逆转录病毒疗法（ART）为 一旦被感染，尽可能尽可能早，联合国联合国艾滋病毒和艾滋病（UNAID）称 用于全球艾滋病毒测试，治疗和病毒抑制的增加。但是，因为很大一部分 个人没有意识到自己的感染，扩大测试能力具有很高的潜力 未经测试的高风险人群。可以直接检测HIV病毒血症的当前护理设备也是如此 昂贵，需要一定程度的专业培训才能进行操作。而且，许多POC技术具有 我们获得的批准不足以在峰值病毒血症和急性感染中传播期间检测HIV。 现有的自我测试技术仅检测宿主抗体响应，该抗体响应是在初始几周后产生的 感染。因此，实现分散测试的实用且负担得起的POC测试平台将是 对于联邦“结束艾滋病毒流行：美国计划”倡议至关重要。为此，AI生物科学 开发低成本磁性颗粒（MP）和纳米颗粒的三明治免疫测定的提案 用于与核酸扩增的敏感性的HIV-1 P24衣壳蛋白的早期检测 方法。这个小型设备（〜4x3x2英寸）执行基于MP的P24捕获和浓度，其次是 用抗体修饰的铂纳米颗粒（PTNP）标记。然后，PTNP与氢相互作用 过氧化物溶液以创建一个可以使用低成本电子的信号来创建可以以极高灵敏度记录的信号 成分。我们旨在优化第一阶段的化学和测定表颜料，以制作30分钟的样本 - 需要最少的培训和动手时间的待命测试。我们将与Chuan-Jian Zhong教授合作， 宾厄姆顿大学（BU）的纳米技术和催化专家，以表征和合成 抗体修饰的MPS和PTNP。 AI Biosciences还与乔治的Jeanne Jordan教授合作 华盛顿大学（GWU）协助设备评估和测试。在第一阶段结束时，我们将带来 我们的设备并向她的实验室进行测定以进行技术演示。我们将培训技术人员使用 我们的设备和验证测定法。他们将比较我们的免疫测定结果和PCR和第五 一代免疫测定。如果我们的敏感P24检测方法成功，我们将使用相同的 HIV抗体检测方法。