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.
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.
