Tools that can quickly detect the presence or absence of previously unknown pathogens are critical in an effective defense against future pandemics.
As a first step towards using such tools, the Department of Homeland Security (DHS) Science and Technology Directorate (S&T) is investing in a new technology that can discriminate between bacterial and viral infections using only a single drop of blood per patient.
The hope is that by the time another major biological event—be it intentional, accidental or natural—comes knocking on our door, the United States will be able to quickly triage people for their next step of medical care. With this technology, front line medical personnel could use it to quickly determine the presence of either viral or bacterial infections in people and thereby best protect themselves, triage patients, and clear mass transport passengers for travel.
To make this a reality, S&T is working with the Cross-Border Threat Screening and Supply Chain Defense (CBTS) Center of Excellence and two leading biotechnology companies to develop a virus-versus-bacteria detection/diagnostic platform called the Host Response Test System (HRTS). It comprises a ruggedized portable device that can differentiate between bacterial and viral infections within an hour, even in pre-symptomatic patients. S&T’s main interests in funding the HRTS effort are to help accelerate the development of pathogen-agnostic detection technology and to support interagency partners that have medical authority.
“Long before COVID-19 was on anyone’s radar, S&T saw the importance of conducting better biological surveillance,” said CBTS Director Dr. Gregory Pompelli. “S&T wanted to make sure we had this tool for DHS and others, recognizing that we need better surveillance for biothreats.”
CBTS partnered with two companies: Predigen Inc., which developed the biomarkers that indicate the presence of viruses or bacteria, and Biomeme, Inc., which developed the Franklin™ thermocycler testing instrument to measure those biomarkers.
“Identifying potentially ill passengers and DHS staff sooner means they are less likely to spread infectious diseases and can get treatment earlier,” added CBTS Executive Director Dr. Heather Manley Lillibridge. “The Food and Drug Administration has granted Emergency Use Authorization for the detection of SARS-CoV-2 on the Biomeme instrument. In work performed at Duke University and supported by the National Institutes of Health and the Antibacterial Resistance Leadership Group, the Predigen bacterial/viral tests have been evaluated in 1,200 patients across the U.S. with acute respiratory illness.”
HRTS will help DHS mitigate biological events that impact national security, including those that can negatively impact the national economy, critical infrastructure, or could overwhelm state and local response capabilities. Moreover, HRTS will mitigate the impacts of communicable disease upon the DHS workforce, interagency partners and the public.
“DHS is investing in further development of the Predigen/Biomeme HRTS that can be used in both biodetection systems and medical diagnostics related to homeland security,” said Dr. Lloyd Hough, who leads S&T’s Hazard Awareness and Characterization Technology Center (HAC-TC). “Our civilian population and our economy would benefit greatly if HRTS units were brought closer to where they are needed most. And if the system is widely available, it may help to mitigate a future outbreak and even prevent a pandemic.”
HRTS will quickly identify viral/bacterial infections
When another contagious disease outbreak occurs, medical first responders will again be on the frontlines. HRTS could help first responders screen the population for signs of infection, even if the people being screened are asymptomatic.
“The portability of the technology allows you to use it anywhere,” said Dr. Ephraim Tsalik, chief investigator at Predigen and associate professor of medicine at Duke University. “It serves as a tool to identify people who may be sick and don’t even realize it.”
When someone is exposed to a pathogen, distinct changes in the genes of the immune cells are triggered—changes specific for viral or bacterial infections. HRTS takes advantage of this phenomenon. Specifically, HRTS uses quantitative polymerase chain reaction (PCR) technology to measure the extent to which specific immune-related genes (biomarkers) are turned on or off (gene expression), and these gene expression signatures indicate whether viruses or bacteria are causing an infection. Predigen scientists at Duke University initially identified these biomarkers to detect and distinguish bacterial from viral infections in as little as a single drop of blood. HRTS could also identify someone exposed to a virus but not yet symptomatic. A critical window exists between the time of virus exposure and when someone becomes sick due to the infection, which can be many days. And since a patient’s immune response to the virus is measured and not the virus itself, HRTS is perfectly suited to identify emerging viral infections before tests for that new virus are widely available.
“Since the immune system responds to pathogens within hours of exposure, these biomarkers could be detected days before symptoms appear. This is a far superior screening tool than taking temperatures or other routinely measured symptoms,” said Tsalik. “For the S&T project, we are adapting Biomeme’s thermocycler technology to measure gene expression signatures.”
The Biomeme thermocycler was initially created in 2007 for environmental and veterinary pathogen testing in the field. Over the past decade, it evolved into pre-symptomatic testing. Biomeme and Predigen started working together on HRTS in 2018, and S&T started funding them in April 2020. According to Biomeme, no technology modifications were needed to embark on this HRTS effort.
Biomeme’s thermocycler can simultaneously detect and quantify 27 biomarkers. Predigen’s host response tests requires 24 of these, leaving space for up to three additional targets, including SARS-CoV-2 or the influenza virus. Biomeme and Predigen are currently working on two host response tests for S&T. One, called PreViral, can identify pre-symptomatic viral infection. The second test, called Bacterial/Viral, can discriminate between bacterial and viral infections.
“Although DHS is not involved in human diagnostic development per se, we do have a mission to advance technologies that can be used for biodetection and support the resilience of the U.S. homeland,” said HAC-TC’s Hough. “HRTS advances the technology paradigm for pathogen-agnostic biodetection and diagnosis that might someday be used to support DHS needs in deployed locations.”
“DHS is concerned about the next unknown pathogen that threatens our national health security,” added Hough. “That is why we are supporting the integrated development of the Predigen tests, which can discriminate between viral and bacterial diseases and use reagents suitable for austere environment, and Biomeme’s ruggedized machine, on which these tests are run. In the future, we may be able to push the capabilities of HRTS and its reagents to serve other DHS biodetection needs or even as a screening solution for border security.”
A functional HRTS prototype could be ready within a year
S&T is now halfway through this effort, and researchers are currently optimizing the bacterial and viral signatures and verifying that all the Predigen tests are compatible with the Biomeme instrument, which together comprises the integrated HRTS. Next, CBTS will validate the extent to which the tests distinguish between viral and bacterial infections, as well as identify people who are pre-symptomatic. S&T is also working to ensure an affordable price of HRTS, so it can be widely adopted for screening prior to prescribing antibiotics.
“The partnership with S&T has been very valuable to us,” said Pompelli. “This project is a testament to the value of the S&T policy of investing in good research.”
HRTS could also be useful for other federal agencies. For instance, the Department of Defense could use it to screen troops before deployment, and the National Aeronautics and Space Administration could screen astronauts prior to space shuttle missions. Moreover, Tsalik adds “Once these host response tests have undergone rigorous analytical and clinical validation, they will finally give clinicians the information they need to confidently know when to use antibiotics.”
“The DHS COEs’ focus on basic research is pushing the edge of science and technology to support the homeland security mission,” said Hough. “And this project is a perfect example of that.”