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.

项目概要 NIH SBIR 第一阶段提案的目标是开发一种低成本、快速的即时护理 (POC) p24 测试，用于 早期检测人类免疫缺陷病毒（HIV）感染将适合在分散使用。 发达国家和发展中国家的基础设施和实验室能力有限 禁止基于病毒载量的核酸检测，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，同时提供经过最低限度培训的人员即可操作的设备，显着 世界卫生组织指南建议开始抗逆转录病毒治疗（ART）。 一旦感染，应尽早采取行动，联合国艾滋病毒和艾滋病联合规划署（UNAIDS）已呼吁 然而，全球艾滋病毒检测、治疗和病毒抑制方面的增加占很大比例。 的个人不知道自己受到感染，扩大检测能力很有可能达到以前的水平 目前可以直接检测 HIV 病毒血症的护理点设备也是未经测试的。 昂贵且需要一定程度的专业培训才能操作此外，许多 POC 技术都具有。 已被批准的灵敏度不足以检测病毒血症高峰期间的 HIV 和急性感染的传播能力。 现有的自检技术只能检测宿主抗体反应，该反应在初始抗体反应几周后出现。 因此，实用且负担得起的、能够实现去中心化测试的POC测试平台将成为人们关注的焦点。 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 Biosciences 提出了这一倡议。 提议开发一种基于低成本磁性颗粒（MP）和纳米颗粒的夹心免疫测定法 用于HIV-1 p24衣壳蛋白的早期检测，灵敏度接近核酸扩增 这个小型设备（~4x3x2 英寸）执行基于 MP 的 p24 捕获和浓缩，然后进行。 用抗体修饰的铂纳米颗粒 (PtNP) 进行标记，然后 PtNP 与氢相互作用。 过氧化物溶液产生可以使用低成本电子设备以极高灵敏度记录的信号 我们的目标是在第一阶段优化化学和测定形式因素，以制作 30 分钟的样品。 我们将与 Chuan-Jianzhong 教授合作，以最少的培训和实践时间来回答测试。 宾厄姆顿大学 (BU) 的纳米技术和催化专家，表征并合成了 AI Biosciences 抗体还与乔治大学的 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。 我们将培训技术人员使用我们的设备和检测方法到她的实验室进行技术演示。 他们会将我们的免疫测定结果与 PCR 和第五次测定的结果进行比较。 如果我们的 p24 敏感检测方法成功，我们将使用相同的方法。 HIV抗体检测方法。