BARDA Support to Speed Development of Next-Generation Sequencing-Based Diagnostics Platform
The Center for Infection and Immunity (CII) at Columbia University Mailman School of Public Health is partnering with the Biomedical Advanced Research and Development Authority (BARDA) within the U.S. Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response to speed the development of a viral diagnostic platform that will advance the ability of medical and public health practitioners to detect and respond to emerging infectious diseases early with a precision medicine approach.
BARDA’s Division of Research, Innovation, and Ventures (DRIVe) is collaborating with industry and academic partners, including the CII, to advance the ability to quickly respond to public health emergencies with new diagnostic tests that can detect all known and unknown respiratory viruses. These industry and academic partners will optimize in-house next-generation sequencing (NGS) capabilities for commercial clinical use, by lowering the sample-to-result time to under 24 hours, reducing interference from host RNA, and performing analytical validation of the platform using both contrived and clinical respiratory samples. The goal: faster diagnosis, categorization, and identification of new and emerging pathogens.
Partners will pursue regulatory pathways toward commercialization of the NGS-based diagnostics with support from BARDA. While current applications of this technology are focused on centralized laboratory systems, future applications could include combining diagnostic and biosurveillance together with point-of-care testing.
“VirCapSeq is the only sequencing technology that has the broad range coverage of unbiased high throughput sequencing with significantly greater sensitivity in the detection and identification of all vertebrate viruses, including new and emerging species,” says Vishal Kapoor, MS, deputy director for laboratory medicine at CII. “This technology can help identify novel viral threats early on in a public health emergency with the potential to contain outbreaks and prevent pandemics.”
“Our technology is poised to transform precision medicine, giving caregivers the ability to quickly pinpoint the cause of an infection so as to guide treatment,” says W. Ian Lipkin, MD, John Snow Professor of Epidemiology and CII director. “At the same time, this diagnostic tool will be a boon for public health by providing information on viruses circulating in a community.”
Next-Generation Sequencing-Based Diagnostics
Most of today’s clinical diagnostic tools are designed to detect the presence of a specific and known pathogen. These targeted assays—like the PCR and antigen tests that have become widely used during the COVID-19 pandemic—meet a critical need for diagnostics. Yet targeted diagnostic tests are reactive by design and typically are not available until after an outbreak has begun. Additionally, significant time and effort are needed to develop, verify, and validate such tests and obtain regulatory approval. When faced with a public health emergency of pandemic potential, time is crucial, and having an agnostic diagnostic test—a diagnostic that can identify any known or novel pathogen—can help accelerate a national response.
The standard of care currently is grounded in assessing symptoms and then performing targeted testing for individual viruses. Next-generation sequencing (NGS)-based agnostic diagnostic technology has the potential to change the paradigm of care by leading with a single untargeted diagnostic to detect any and every respiratory pathogen. Therefore, these tests could provide information critical to timely and actionable patient care.
The emergence of another respiratory virus with pandemic potential is highly likely, and public health and response communities will need comprehensive diagnostic tests to quickly detect the next novel pathogen. Accelerating the development of these NGS-based agnostic diagnostics could help bolster U.S. preparedness for future outbreaks and potentially enable other opportunities for infectious disease diagnostics.
This project has been supported in whole or in part by BARDA, part of the HHS Office of the Assistant Secretary for Preparedness and Response, under Contract No. 75A50122C00012.
VirCapSeq is a positive selection system that allows simultaneous detection, differentiation and discovery of vertebrate viruses. The system is driven by bead-anchored oligoes that are designed to bind and capture nucleic acids from all known vertebrate viruses. It was developed in the Center for Infection and Immunity (CII) and is patented by Columbia University. A 2015 study reported that the method resulted in 100 to 10,000-fold increases in sensitivity compared to conventional high-throughput tests. The test has been used in studies of type 1 diabetes in Australia, respiratory disease in Uganda, unexplained illness in Tanzania, and chikungunya in Brazil.
VirCapSeq is a New York State-approved diagnostic test for the detection of nucleic acids of both DNA and RNA viruses in blood samples. Going forward, CII scientists will validate the technology to detect viruses in respiratory samples. Additionally, they will also make the test available with portable sequencers for point of care and biosurveillance use.