DISCLAIMER: Included references to commercial products does not constitute endorsement by the U.S. Department of Defense or the JPEO-CBRND.
The year 2020 will undoubtedly be remembered as the year of the pandemic; the year the world was turned upside down by COVID-19. However, lurking in the shadows and out of the limelight, another viral outbreak plagued the western Équateur Province in Africa’s Democratic Republic of the Congo (DRC), with its own potential for global devastation if given the opportunity to cross international borders. An old and recurrent viral monster, the Ebola virus (EBOV) made both its 10th and 11th appearances on record in the DRC from 2018 to 2020, and the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) was at the forefront of the Department of Defense’s (DOD) response efforts to combat it.
The EBOV has proven itself to be one of the most deadly viruses known to mankind. Touting an exceptionally high mortality rate, between 70-90 percent, books and movies fill our shelves, dedicated to telling its terrifying story. As the origin of EBOV is still yet to be found, the virus remains a recurring danger, and each reemergence seems to bring with it its own unique set of challenges. Yet, merely six months after the most recent 2020 EBOV outbreak was identified, it was officially declared over by the Minister of Health of the DRC. Successful rapid response to this latest outbreak did not happen by chance. Control over this outbreak was only possible thanks to the groundwork laid by an intricate network of organizations, through years of coordination of efforts.
“Novelists and screenwriters would have a difficult time coming up with something more horrifying than the filovirus, Ebola,” said Charles Paschal, Assistant Program Manager for the JPEO-CBRND’s Joint Project Manager for Chemical, Biological, Radiological, and Nuclear Medical (JPM CBRN Medical). “I don’t think people realize the terrible monster that barely made it out of its cave.”
The DOD has a long-standing history of developing medical countermeasures to combat deadly biological threats, and the JPM CBRN Medical’s fingerprints can be found all over its Ebola response efforts. The JPM CBRN Medical organization is dedicated to developing and delivering medical countermeasure solutions to diagnose, treat, and protect our nation’s warfighters from CBRN threats, to include weaponized biological or naturally-occurring agents like EBOV. Through a three-pronged, full-spectrum program approach, the approach is to attack threats at every angle: through diagnostic program efforts dedicated to delivering early identification solutions (see it), therapeutic program efforts dedicated to delivering treatment solutions (treat it), and vaccine program efforts dedicated to delivering solutions to prevent infection (prevent it).
When dealing with any CBRN threat, you must first be able to see it.
The world has known about these filoviruses since the 1970’s, but according to Paschal, the 1989 ‘Ebola Reston’ incident is what really “changed the game.” The events of the 1989 EBOV outbreak in Reston, Virginia - which inspired the 1994 best-selling nonfiction novel “The Hot Zone” and subsequently led to the creation of the 1995 movie blockbuster “Outbreak” - undoubtedly captured the world’s attention; and although exaggerated and “creatively adapted,” as all Hollywood movies are, both the novel and movie did manage to inspire an awareness and fear of the all-too-real virus. The later 2014-2016 West Africa Ebola outbreak, the first and largest epidemic of its kind, was yet another wake-up call that made clear the danger EBOV disease (EVD) posed to not just U.S. national security interests abroad, but to the U.S. domestic population in the event of a pandemic. The worlds eyes were opened to just how important proactive preparation would be to mitigating future occurrences; reinforcing the dire need for both an efficacious vaccine against highly-pathogenic filoviruses like EBOV, and diagnostic capabilities to identify it.
The importance of diagnostic capabilities cannot be overstated when it comes to infectious disease response efforts, and the DOD-funded Warrior Panel diagnostic test was the JPM CBRN Medical’s first blow against EBOV. The JPM CBRN Medical’s established partnership with BioFire Defense, LLC, resulted in development of the Next Generation Diagnostics System 1 (NGDS 1), known commercially as the BioFire® FilmArray®, a diagnostic tool used in hospitals and clinical settings around the world, including the Centers for Disease Control and Prevention (CDC) Laboratory Response Network. From that initial collaborative effort came the U.S. Food and Drug Administration (FDA)-approved Warrior Panel, used in conjunction with the BioFire® FilmArray®, for the diagnosis of anthrax, tularemia, plague, Q fever, and hemorrhagic fevers caused by Ebola and Marburg viruses.
Once you are able to see the threat, you must have the capabilities in place to treat it.
Following the 2014 EBOV outbreak, there was also advocacy for the capability to execute clinical trials in an outbreak setting, which led to the JPEO-CBRND’s establishment of the Joint Mobile Emerging Disease Intervention Clinical Capability (JMEDICC) facility at Fort Portal Regional Referral Hospital in Western Uganda. The JMEDICC project had a primary objective of establishing the technical capability to execute Phase II clinical trials during outbreaks of high-consequence pathogens, like EBOV. Establishment of the JMEDICC facility in 2016 enabled and trained partners to have the capability to rapidly diagnose, isolate, and treat individuals with EVD, as close as possible to the outbreak, with medical countermeasures in clinical research settings; under appropriate Institutional Review Board approvals and all applicable law and regulatory requirements. Thanks to the JMEDICC facility - which utilized the latest JPM CBRN Medical’s NGDS technology, to include the newly-developed Ebola panels - responders were able to better track the spread of EBOV outbreaks, which was a key component of outbreak response in the area. The facility met the DOD’s intent for foreign humanitarian assistance, supporting Uganda while also providing a unique opportunity to conduct research during outbreak response.
Once you see and understand the threat, you can finally develop and deliver solutions to prevent it.
Fast forward to December 20, 2019, the FDA announced the approval of the first FDA-approved vaccine for the prevention of EVD: Merck & Co.’s Ervebo®. The FDA’s approval of Ervebo® was the result of nearly two decades of efforts by a host of teams across both the public and private sectors. The approval was a major leap forward in protecting both the warfighter and civilian populations from EVD, as well as advancing U.S. government (USG) preparedness efforts.
“I really don’t think anyone realizes that we just defeated the most deadly virus known to man in all of human history,” said Paschal. “Ebola is a monster the likes of which has never been seen before. But now, in 2021, we have an FDA-approved vaccine against it. That’s pretty remarkable.”
Ervebo® had been in development since the 2014-2016 EBOV outbreak in West Africa, and the JPM CBRN Medical’s filovirus vaccine program played a key role in its development, providing funding and technical expertise for non-clinical studies and the immunological assays used for testing in clinical trials. The filovirus vaccine program provided access and substantial support to the DOD-led Filovirus Animal Non-Clinical Group (FANG) Zaire Ebolavirus (EBOV) Enzyme-Linked Immunosorbent Assay (ELISA) (Master File 16537), which was used extensively in multiple clinical trials examining Ervebo® safety and efficacy. Data from these clinical trials was critical to ultimate approval of Ervebo® by both the FDA and the European Commission.
The JPM CBRN Medical’s ability to respond quickly to support the USG’s response to the 2014-2016 outbreak, as well as ongoing collaborative efforts that supported both European Union and U.S. FDA approval of Ervebo®, highlight the value of critical partnerships within the CBRN defense enterprise. This strong community of collaboration also supported development of Gilead Sciences, Inc.’s, antiviral therapeutic remdesivir (Veklury®), which received FDA approval for the treatment of hospitalized COVID-19 patients in October 2020. Furthermore, in December 2020, FDA approval of Ebanga® (formerly mAb114) was announced for the treatment of EBOV; whose original mAb114 antibody was made possible through collaborative funding between the JPEO-CBRND and the Defense Advanced Research Projects Agency (DARPA), and manufactured for DOD personnel at the JPEO-CBRND’s Advanced Development and Manufacturing Facility.
Without a doubt, interagency partnership from the beginning has been vital to both vaccine development efforts and EBOV outbreak response as a whole. Most recent swift triumph over the late 2020 EBOV outbreak showcased that, together, we can overcome any health challenge; as overcoming one of the world’s most dangerous pathogens in remote and hard-to-access communities demonstrates just what is possible when science and solidarity come together.
“No one organization working within the CBRN space can possibly do it alone,” said Col. Ryan Eckmeier, Joint Project Manager for CBRN Medical. “It is critical that we leverage the expertise and resources of our like-minded partners to address not only biological and chemical threats faced by our service members, but also emerging infectious diseases like EVD. Working alongside our partners to continue the fight against the EBOV is a necessary action to reduce the spread of the disease, and the rapid coordination of efforts over the last decade highlights the value of the CBRN defense enterprise and is a testament to the work that we can accomplish together.”
Over the past decade, there has been a noticeable increase in infectious disease outbreaks worldwide. Global health officials agree that it is vital to stop disease outbreaks at their source, and in the midst of the current global COVID-19 pandemic, the world now knows the true threat infectious disease outbreaks pose to our daily lives. 2020 showed just how debilitating a pandemic can be when dealing with a virus touting a mere two percent mortality rate; imagine the damage a virus with Ebola’s 70-90 percent mortality rate could do. The fight is far from over, but as biology continues to evolve, so too does the JPM CBRN Medical and the race to develop protection against that evolution.