An Ultrasensitive and Low-Cost p24 Antigen Test for the Early Detection of HIV

PROJECT SUMMARY The goal of this NIH SBIR Phase I proposal is to develop a low-cost and rapid point-of-care (POC) p24 test for early detection of human immunodeficiency virus (HIV) infection. It will be appropriate for use at decentralized settings in developed and developing countries where the limitations of infrastructure and laboratory capability prohibit viral load-based nucleic acid testing. Our aim is to maintain the accuracy and sensitivity of traditional lab-based diagnostics while providing a device that a minimally trained person can operate, significantly increasing access to HIV diagnostics. The WHO guidelines recommend initiating antiretroviral therapy (ART) as early as possible once infected, and the Joint United Nations Programme on HIV and AIDS (UNAIDS) has called for global increases in HIV testing, treatment, and viral suppression. However, because a significant proportion of individuals are unaware of their infection, expanding testing capabilities has a high potential to reach previously untested high-risk populations. Current point-of-care devices that can detect HIV viremia directly are too expensive and require some level of specialized training to operate. Also, many POC technologies that have been approved are not sensitive enough to detect HIV during peak viremia and transmissibility in acute infection. Existing self-testing technologies only detect the host antibody response, which arises weeks after the initial infection. Therefore, practical and affordable POC test platforms that enable decentralized testing will be important for the federal “Ending the HIV Epidemic: A Plan for America” initiative. To this end, AI Biosciences proposes to develop a low-cost magnetic particle (MP) and nanoparticle based sandwich immunoassay that can be used for the early-detection of HIV-1 p24 capsid protein with a sensitivity near that of nucleic acid amplification approaches. This small device (~4x3x2 inches) performs MP-based p24 capture and concentration, followed by labeling with antibody-modified platinum nanoparticles (PtNPs). The PtNPs then interact with a hydrogen peroxide solution to create a signal that can be recorded with extremely high sensitivity using low-cost electronic components. We aim to optimize the chemistry and assay form factor during Phase I to make a 30-min sample- to-answer test that requires minimal training and hands-on time. We will work with Professor Chuan-Jian Zhong, a nanotechnology and catalysis expert at Binghamton University (BU), to characterize and synthesize the antibody modified MPs and PtNPs. AI Biosciences has also partnered with Professor Jeanne Jordan of George Washington University (GWU)to assist with device evaluation and testing. At the end of Phase I, we will bring our device and assay to her laboratory to perform a technology demonstration. We will train technicians to use our device and assay for validation. They will compare the results from our immunoassay to PCR and 5th generation immunoassays. If our approach for sensitive p24 detection is successful, we will use the same approach for HIV antibody detection.