Diagnostics, Biosurveillance, Vaccines and Therapeutics Support Public Health
A recent report in The US Army War College Quarterly: Parameters, titled “Responding to Future Pandemics: Biosecurity Implications and Defense Considerations,” profiles three key factors the U.S. Department of Defense believes “have complicated” the landscape of biodefense threats. The piece notes that “In an evolving and expanding biothreat landscape caused by emerging biotechnologies, increases in global infectious disease outbreaks, and geopolitical instability, the Department of Defense now faces challenges that alter its traditional approach to biothreats and prompt the need for modernized, improved preparedness for – and response to – potential biothreat scenarios.”
It’s a stark reality that has been steadily addressed for decades by MRIGlobal innovations
Threat Detection Diagnostics
Outliers in the standard diagnostics space, the biothreat organisms that cause anthrax (Bacillus anthracis), tularemia (Francisella tularensis), glanders (Burkholderia mallei), melioidosis (Burkholderia pseudomallei), plague (Yersinia pestis), and typhus (Rickettsia prowazekii) are not circulating in the population. If an outbreak were to occur – due to a bioterror attack, for example – accurate and rapid testing would be crucial. If not detected and treated promptly, infections from these pathogens can result in mortality rates of anywhere from 40-90 percent.
T2 Biosystems, an emerging leader in in vitro diagnostics, has been working to develop the T2Biothreat Panel, which is a fully-automated, direct-from-blood test designed to run on the T2Dx® Instrument and simultaneously detects these six biothreat pathogens, with funding support from BARDA.
Because we specialize in work with biothreat pathogens, MRIGlobal supported T2 Biosystems during the panel’s clinical trial, contriving 350 positive samples in our BSL-3 laboratory. Using these samples, the trial demonstrated very high sensitivity and specificity across all six targets, supporting validation of positive samples. This then enabled completion of clinical evaluation of T2’s rapid assay to detect these six biothreat organisms, which was designed to support a U.S. Food and Drug Administration (FDA) submission. Once approved, the T2Biothreat Panel can detect the aforementioned biothreat pathogens within four hours, providing clinicians the necessary information to appropriately and rapidly treat infected patients.
Improvements to Biothreat Detection
In the field of biodefense and especially during possible biothreat events, false negative and false positive testing results have serious consequences. The adoption of amplicon sequencing (AS) for biosurveillance because it enables discrimination of true positives from near-neighbor false positives, as well as broad, simultaneous detection of many targets in many pathogens in a high-throughput scheme. However, the high sensitivity of AS can lead to false positives. In a recent paper published with collaborators, we describe how appropriate controls and workflow reporting can help address the challenges associated with AS, with the goal of providing greater accuracy in results during biothreat incidents.
Our Work with the Biothreat Anthrax
Following the 9/11 attacks and the October 2001 anthrax letter attacks, US government officials reached out to MRIGlobal about establishing a rapid response laboratory capability in the National Capital Region (NCR) for the surveillance and detection of biological threat agents, including anthrax. This initial call was the beginning of a program that has grown to support several clients and government agencies, serving as an enduring capability and asset to national security for the past two decades.
Our work involving these and other pathogens takes place in our world-class laboratories, including those that are BSL-3, which are considered High-Containment Biosecurity Laboratories (HCBLs). They will continue to be a critically important tool for responding to biothreats and also in infectious disease surveillance programs that support tracking and predicting patterns and trends of infectious disease to augment preparedness and readiness.
During the COVID-19 pandemic, the work in these laboratories also helped move several diagnostic devices through the Food and Drug Administration’s (FDA) Emergency Use Authorization (EUA) process, enhancing the commercial availability of COVID-19 diagnostic products. This work has demonstrated the strength of our laboratory diagnostic capabilities and ability to scale up operations during surge demands like those we have led since the beginning of the pandemic.
Increases in Global Infectious Disease Outbreaks
Diseases – Old and New – Further Cooperation is Required
In just the past six months, populations around the world have been impacted by a series of emerging infectious disease threats that include Marburg, Ebola, and mpox, just to name a few. Never mind that COVID-19 (the disease resulting from SARS-CoV-2) continues to kill approximately 1,000 people in the U.S. alone (as of May 3, 2023) each week, while diseases like tuberculosis and malaria also continue to infect and kill people around the world. While infectious diseases aren’t new, where, how, and sometimes even which diseases are emerging to threaten public health are all evolving. Due to global trade and travel, climate change, and other factors, the risks have increased substantially in recent decades. And it is only a matter of time until a new one emerges to threaten human health.
MRIGlobal has a legacy of supporting global health security across many U.S. government-funded projects to enhance biosafety and biosecurity measures, cooperative research, and biosurveillance of infectious diseases. Our work has helped build laboratory capability and capacity for partner country scientists in West Africa (Guinea, Liberia, Sierra Leone, Senegal), Kazakhstan, and other former Soviet republics.
We have also shared our expertise on enhancing global health security in the Latin American region. When combined with geopolitical, socioeconomic, and environmental factors, especially climate change and human migration, which are expanding the range of disease vectors and pathogens, the risk for infectious disease outbreaks greatly increases. Enhancing global health security requires greater awareness and cooperation within the region, more effective infectious disease surveillance systems, and further investment.
Next generation of Detecting Infectious Diseases
To mitigate the impact of these and other threats, innovative tools are necessary. In collaboration with partners, we are working to design, develop, prototype, and deploy a CRISPR-based diagnostic technology that will provide next-generation detection for our customer, combining gene-editing technology with fieldable diagnostics and biosurveillance. This is a massively multiplexed detection (MMD) device for 1,000 or more targets in a variety of different sample types, including respiratory, soil, serum, and vector-borne.
The goal is for this MMD device to be simple to operate, low-cost, and rapidly reconfigurable to provide high-impact, high-quality, and trusted information that enhances decision-making and concomitant action. Our innovative work aims to leverage advances in gene editing technologies to develop field-forward diagnostic and biosurveillance technology that enables rapid detection of zoonotic and other viruses, bacteria, host biomarkers, and other diseases, anytime, anywhere. As a result, it will improve the speed and efficacy of triage and treatment, thus augmenting the standard of care for the military and public health domains in austere environments.
Despite the production of hundreds of different tests from manufacturers around the world, testing demands and genotyping needs in response to the SARS-CoV-2 pandemic have not been met due to high demand and limited availability, especially in more remote areas of the world. Further, the equipment and expertise required to genotype isolates via whole genome sequencing makes this capability entirely out-of-reach in many low-resource locations. Delayed test results have also made it difficult to determine the best course of treatment in a timely manner, and further delay the tracing and isolation of infected persons to prevent secondary transmissions. Each of these barriers – access, quantity, and testing delays – has resulted in increased disease among more people, prolonging the pandemic.
In a breakthrough for SARS-COV-2 diagnostics, MRIGlobal played a key role in research on the design, development, testing, and validation of a multiplex panel that detects five major variants of concern – Alpha, Beta, Gamma, Delta, and Omicron – on a portable platform. This advancement will enable extended availability of rapid, accessible, and portable genotyping capabilities to low resource settings around the world, as the assays provide quick results, can be stored at room temperature, and are utilized on handheld PCR devices.
We also offer government and commercial clients services that expand and accelerate delivery of high quality clinical diagnostic products, including assay design, diagnostic and detection device development, analytical verification, and clinical validation through regulatory submission. We provide extensive research and product development expertise; facilities, analytical services, clinical trial site, and clinical trial services and support; and regulatory guidance to support FDA, EUA, and 510(k) submission filings. It is these in vitro diagnostic development services that help rapidly develop and commercialize new and disruptive diagnostic technologies and tools.
Accelerating Development of Diagnostics
Emerging and novel biothreats and infectious disease threats pose a constant challenge, as effective biodetection of these threats is often a race against time. Driven by consumer demand, a surge of In Vitro Diagnostic (IVD) tools are coming to the market, providing diagnoses at the point-of-care. Our team at MRIGlobal has proposed an IVD development lifecycle that should accelerate their path from conceptualization to market. By doing so, we will enable significant improvements in the future of diagnostics and their impact on the practices of laboratory medicine, public health, and healthcare delivery.
New Laboratory Supports 510(k) Approvals
Citing customer interest in achieving permanent market access through FDA’s 510(k) approval process, enabling market approval and access for their products, we have opened a new lab developed specifically for this purpose. It was designed to host the Roche Diagnostics cobas® 6800, which is a fully automated, highly sensitive, sample to answer platform capable of running more than 20 Roche diagnostic assays. These include respiratory, blood-borne disease, sexual health, and transplant assays.
This instrumentation, in combination with our Hologic Panther Fusion® and other FDA cleared molecular diagnostic platforms, enables our customers access to high quality assays in a very timely manner and the flexibility to work on many different diseases and evaluate a variety of different products, including antigen tests and full-size sample enhancer molecular tests. This will help our customers prepare for the future and address whatever the next emerging infectious disease is.
Vaccines and Therapeutics
Our team has a depth of experience testing and developing vaccines and therapeutics for use against infectious disease threats. Because we have immediate access to world-class laboratories, we are uniquely positioned to start working with emerging infectious diseases rapidly, as we did with SARS-CoV2 (COVID-19) beginning in early 2020. We are also registered to work with select agents and toxins, including a subset of tier 1 select agents, such as highly pathogenic avian influenza and mpox. This ability to work with a broad range of pathogens supports therapeutics testing and development for small commercial clients in need guidance and government agencies experienced with established practices.
Developing solutions to address the world’s most important and challenging biothreats and infectious diseases is what we do. Every single day, our commitment to our customers is to provide unsurpassed technical expertise, world-class laboratories, and a partnership to find customized solutions to your specific challenges.
GETTING STARTED AT MRIGLOBAL
Contact MRIGlobal for further information about our work with biothreats and infectious diseases. Through an interdisciplinary approach, we provide scientific and subject matter expertise for development of medical countermeasures research against specific threats, while expanding and accelerating the delivery of high quality clinical diagnostic products.
To discuss how we can help your project be successful, contact us today.
SIGN UP FOR OUR NEWSLETTER
Sign up for the MRIGlobal newsletter! It’s the best way to get the latest updates in the world of applied scientific engineering research delivered directly to your inbox.