Point-of-Care HIV Antigen/Antibody Diagnostic Device

描述(由申请人提供)：mBio诊断公司建议开发一种低成本、护理点(POC)、HIV-1抗原/抗体组合诊断设备。目标是让Ag/AbComo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，以及广泛使用的HIV快速检测的成本和工作流程。这项第一阶段的提案将专注于开发一种新的、多粒子方法，用于HIV-1p24抗原夹心免疫分析，该方法将提供临床相关的检测极限。在第二阶段，p24检测将与mBio的多路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组合检测将成为现有的最灵敏的POC HIV筛查技术。艾滋病毒感染仍然是美国和世界范围内的一大公共卫生危机。人们越来越意识到，严重感染的人不成比例地促进了疾病的传播。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病毒抗原的护理点(POC)测试。一种廉价、易用、POC格式的HIV-1抗原/抗体(Ag/Ab)组合分析--即所谓的“第四代”免疫分析--将从根本上改进美国和世界各地的HIV-1筛查工作。这项建议的具体目标是：(1)建立一个具有良好特征的临床血清/血浆样本的核心集合，重点是急性和最近的艾滋病毒感染。第一阶段的收藏将基于现有档案和来源的样本，并根据本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抗原检测的模型试验标准曲线，其检测下限为20pg/mL。(3)定量比较AIM 1新近感染分组和金标准方法的mBio抗原/抗体检测结果。这一目标的里程碑是对目前市场领先的FDA批准的HIV-1/2快速检测没有检测到的HIV-1阳性样本的80%进行检测。在成功完成第一阶段项目后，将在第二阶段提出设备工程和导致FDA研究设备豁免(IDE)的更大临床验证。 公共卫生相关性：拟议的护理点(POC)HIV-1Ag/Ab组合诊断设备将填补对艾滋病毒筛查技术的关键需求，该技术可检测最近和急性感染的个人。这项技术将用于美国和世界各地的公共卫生实验室、性病诊所、城市急救部门、有针对性的外展项目等的多重测试算法。

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.