Point-of-Care HIV Antigen/Antibody Diagnostic Device

描述（由申请人提供）：MBio Diagnostics, Inc.提议开发一种低成本，即时护理（POC）， HIV-1抗原/抗体组合诊断设备。目标是使抗原/抗体组合系统在POC平台上提供基于实验室的第四代抗原/抗体临床分析仪的性能，该平台具有广泛使用的艾滋病毒快速检测的成本和工作流程。该I期提案将侧重于开发一种用于HIV-1 p24抗原夹心免疫测定的新型多粒子方法，该方法将提供临床相关的检测限。在II期，p24检测将与MBio的多重HIV-1/2抗体检测系统相结合。如果成功，由此产生的最小仪器化Ag/Ab联合检测将是最敏感的POC HIV筛查技术。艾滋病毒感染仍然是美国乃至全世界的一个重大公共卫生危机。越来越多的人认识到，急性感染者不成比例地促进了疾病的传播。然而，这些个体仍然是最难识别的，因为在作为血清学诊断基础的HIV抗体出现之前，传染性是最高的。目前还没有fda批准的直接针对HIV病毒抗原的即时检测（POC）。HIV-1抗原/抗体（Ag/Ab）联合测定——所谓的“第四代”免疫测定——价格低廉，使用简单，POC格式将从根本上改善美国和全世界的HIV-1筛查工作。该提案的具体目标是：(1)建立一个具有良好特征的临床血清/血浆样本的核心收集，重点是急性和近期HIV感染。第一阶段的收集将基于现有档案和来源的样品，并根据该合同进行额外的测试。第一阶段的里程碑将是收集60份HIV-1阳性血清和40份阴性血清。(2)展示MBio的磁性多粒子方法用于快速、超灵敏、无酶检测HIV p24抗原。这一目标的里程碑是p24抗原检测的模型分析标准曲线，检测下限为20 pg/mL。(3)定量比较MBio抗原/抗体测定在Aim 1近期感染组上与金标准方法的性能。这一目标的里程碑是检测80%的HIV-1阳性样本，而目前市场上领先的fda批准的HIV-1/2快速检测无法检测到。在I期项目成功完成后，将在II期提出器械工程和更大的临床验证，从而获得FDA研究性器械豁免（IDE）。

DESCRIPTION (provided by applicant): MBio Diagnostics, Inc. proposes to develop a low-cost, point-of-care (POC), HIV-1 antigen/antibody combination diagnostic device. The goal is for the Ag/Ab combo system to deliver the performance of laboratory based, 4th generation antigen/antibody clinical analyzers, in a POC platform with cost and workflow of the widely used HIV rapid tests. This Phase I proposal will focus on development of a novel, multiple particle approach for a HIV-1 p24 antigen sandwich immunoassay that will deliver clinically relevant limits of detection. During Phase II, the p24 assay will combined with MBio's multiplexed HIV-1/2 antibody detection system. If successful, the resulting minimally instrumented Ag/Ab combination assay would be the most sensitive POC HIV screening technology available. HIV infection remains a major public health crisis both in the United States and worldwide. There is increasing awareness that acutely infected individuals disproportionately contribute to disease spread. Yet these individuals remain the most difficult to identify, as infectivity is highest prior to the appearance of the HIV antibodies that serve as the basis for serological diagnostics. There are currently no FDA-approved point-of-care (POC) tests that directly target HIV viral antigens. An HIV-1 antigen/antibody (Ag/Ab) combination assay - the so-called "4th generation" immunoassay - in an inexpensive, simple to use, POC format would fundamentally improve HIV-1 screening efforts in the United States and worldwide. The specific aims of this proposal are to: (1) Establish a core collection of well characterized clinical serum/plasma samples focused on acute and recent HIV infection. The Phase I collection will be based on samples from existing archives and sources, with additional testing under this award. The Phase I milestone will be a collection of 60 HIV-1 positive and 40 negative sera. (2) Demonstrate MBio's magnetic multi-particle approach for rapid, ultra-sensitive, no- enzyme detection of HIV p24 antigen. The milestone for this aim is a model assay standard curve for p24 antigen detection with a lower limit of detection of 20 pg/mL. (3) Quantitatively compare performance of the MBio antigen/antibody assay on the Aim 1 recent infection panel with gold-standard methods. The milestone for this aim is detection of 80% of HIV-1 positive samples not detected with the current market- leading FDA-approved HIV-1/2 rapid test. Upon successful completion of the Phase I project, device engineering and a larger clinical validation leading to an FDA investigational device exemption (IDE) will be proposed under Phase II. PUBLIC HEALTH RELEVANCE: The proposed point-of-care (POC) HIV-1 Ag/Ab combination diagnostic device will fill a critical unmet need for HIV screening technologies that detect recent and acutely infected individuals. The technology will be used in multi-test algorithms in public health laboratories, STD clinics, urban emergency departments, targeted outreach programs,etc., both in the United States and worldwide.