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-1/2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。第一阶段的研发达到或超过了规定的技术里程碑。特别是，mBio HIV抗原和抗体检测提供的综合性能大大超过FDA批准的快速检测，并提供与更复杂的基于实验室的检测几乎相同的性能。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。这项建议的具体目的是：(1)将第一阶段p24抗原检测分析与mBio多路血清学分析试剂盒相结合，解决最终单抗(MAb)对选择、HIV-1抗原和HIV-2抗原选择、试剂结合、交叉反应以及将分析步骤和复杂性降至最低的问题。(2)修改mBio试剂盒、机架、阅读器和软件，以提供自动的HIV-1/2Ag/Ab组合结果，并将热稳定性分析试剂纳入MQ试剂盒。AIM 2里程碑是为临床合作者提供的便携式集成系统，满足FDA CLIA豁免指南要求。(3)使用特征良好的早期HIV感染样本验证系统，包括由20个急性感染样本、早期血清转换和血清阳性样本组成的200个HIV阳性样本小组。将使用200个HIV阴性样本进行特异性检测。(4)将系统放置在预期使用环境中，并在设计锁之前捕获操作和可用性反馈，并使用此站点生成关于毛细血管全血样本的初步数据集。该计划的结果将是在临床试验之前为FDA研究设备豁免(IDE)会议提供系统设计和数据集。

DESCRIPTION (provided by applicant): MBio Diagnostics, Inc. proposes to develop a low-cost, point-of-care (POC), HIV-1/2 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. Phase I research and development met or exceeded stated technical milestones. In particular, the MBio HIV antigen and antibody assays provided a combined performance that significantly exceeds performance FDA approved rapid tests, and provides near equivalence to much more complicated laboratory based tests. 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) Combine the Phase I p24 antigen detection assay with the MBio multiplexed serology assay cartridge, addressing issues of final monoclonal antibody (mAb) pair selection, HIV-1 Ag and HIV-2 Ag selection, reagent conjugations, cross-reactivity, and minimization of assay steps and complexity. (2) Modify the MBio Cartridge, Rack, Reader, and Software to deliver an automated HIV-1/2 Ag/Ab combo result, and incorporate heat stable assay reagents into the MQ cartridge. The Aim 2 milestone is a portable, integrated system delivered to clinical collaborators that meets FDA CLIA waiver guidance requirements. (3) Validate system using well characterized early HIV infection specimens including a panel of 200 HIV positive specimens comprised of 20 acute infection samples, early seroconversion, and seropositive samples. 200 HIV-negative samples will be used for specificity testing. (4) Place systems in an intended use setting and capture operational and usability feedback in advance of design lock, and to use this site to generate a preliminary dataset on capillary whole blood samples. The outcome of this program will be a system design and dataset for an FDA investigational device exemption (IDE) meeting in advance of clinical trials.