Integrated point-of-care diagnostic and data reporting platform for emerging arboviruses

SummaryOver 2 billion people live in areas that are affected by the transmission of arthropod-borne viruses (arboviruses) such as the flaviviruses dengue (DENV) and Zika (ZIKV), and the alphavirus chikungunya (CHIKV). These arboviruses are pathogenic and cause millions of infections annually. While the surveillance is critical to understanding infection rates, controlling outbreaks, and informing patient therapeutic efforts, there is no FDA- approved method to simultaneously detect multiple arboviral antigens at the point-of-care and analyze, document, and report data in real-time. In Phase I, we developed non-multiplexed tests for pan-DENV nonstructural protein 1 (NS1), ZIKV NS1, and CHIKV envelope (E) (SimPlex) and a 3-in-1, multiplexed test for all three viral antigens (3Plex). These tests were evaluated in the laboratory and using archived, de-identified patient samples. Additionally, we developed a mobile smartphone application to image capture test results, geo- locate where the image was captured, and upload the data to a central server for epidemiological mapping. In Phase II, we propose to finalize development of the SimPlex and 3Plex tests and enhance our digital platform for real-time metadata reporting to support therapeutic intervention and outbreak management. Our proposed SimPlex and 3Plex tests are low-cost, point-of-care tests that can be done in the field without moving parts, or the necessity of trained personnel, expensive equipment, or a centralized laboratory. In Aim 1, we will scale up production of lead monoclonal antibodies specific for DENV, ZIKV, and CHIKV antigens. In Aim 2, we will optimize SimPlex and 3Plex tests for whole blood detection of DENV, ZIKV, and CHIKV antigens. In Aim 3, we will produce multiple lots of SimPlex and 3Plex tests under GMP for pre-clinical evaluation using prospectively collected samples in Colombia and Brazil. In Aim 4, we will develop and informatic healthcare databased for fast integration of SimPlex and 3Plex test result data with electronic health record repositories; the digital platform will be evaluated in Colombia and Brazil. This project is innovative because it is the first platform that allows point-of-care arboviral antigen-based detection and real-time data analytics for infection geotagging and outbreak management. Upon successful completion of this Phase II project, we will have developed a first-of- its-kind platform, which provides an all-in-one solution to arboviral detection and data reporting, that will be ready for regulatory validation.NarrativeTo monitor viral infections and control emerging outbreaks, a diagnostic test that can simultaneously detect among multiple viruses at the point-of-care, and a platform to report data in real-time is essential. E25Bio Inc. will generate a first-of-its-kind lateral flow antigen-based test to simultaneously detect dengue, Zika, and chikungunya and integrate it with an evidence-based epidemiological and clinical decision support system. This viral detection and data reporting platform will be a simple, yet powerful tool at the disposal of infected individuals and their healthcare providers and organizations responsible for outbreak management.