Point-of-Care HIV Antigen/Antibody Diagnostic Device

描述（由申请人提供）：MBio Diagnostics，Inc.提出开发一种低成本的即时（POC）HIV-1抗原/抗体组合诊断装置。Ag/Ab combo系统的目标是在POC平台中提供基于实验室的第四代抗原/抗体临床分析仪的性能，其成本和工作流程与广泛使用的HIV快速检测相同。该I期提案将专注于开发一种用于HIV-1 p24抗原夹心免疫测定的新型多颗粒方法，该方法将提供临床相关的检测限。在第二阶段，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，所产生的最小仪器Ag/Ab组合检测将是最灵敏的POC HIV筛查技术。艾滋病毒感染仍然是美国和全世界的一个重大公共卫生危机。人们越来越认识到，急性感染者对疾病传播的贡献不成比例。然而，这些人仍然是最难识别的，因为在作为血清学诊断基础的艾滋病毒抗体出现之前，传染性最高。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）组合检测-所谓的“第四代”免疫测定-以廉价，简单易用的POC形式将从根本上改善美国和世界范围内的HIV-1筛查工作。该提案的具体目标是：（1）建立一个集中于急性和近期艾滋病毒感染的充分表征的临床血清/血浆样本的核心收集库。第一阶段的收集将基于现有档案和来源的样本，并根据该奖项进行额外的测试。第一阶段的里程碑将是收集60份HIV-1阳性和40份阴性血清。(2)展示MBio的磁性多颗粒方法，用于快速、超灵敏、无酶检测HIV p24抗原。这一目标的里程碑是用于p24抗原检测的模型测定标准曲线，检测下限为20 pg/mL。(3)定量比较MBio抗原/抗体检测试剂盒在Aim 1近期感染样本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，这些样本是目前市场领先的FDA批准的HIV-1/2快速检测试剂盒未检测到的。成功完成I期项目后，将在II期项目中提出器械工程和更大规模的临床确认，从而获得FDA试验用器械豁免（IDE）。 公共卫生相关性：拟议的床旁（POC）HIV-1 Ag/Ab组合诊断设备将填补HIV筛查技术的关键未满足需求，以检测近期和急性感染的个体。该技术将用于公共卫生实验室，性病诊所，城市急诊室，有针对性的外展计划等的多测试算法，无论是在美国还是全世界。

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.