Products supported by BARDA used to halt 2021 outbreaks
June 21, 2021
Ever since the 1918 pandemic influenza outbreak, public health scientists have sought to identify emerging infections and control them before major outbreaks occur. The principles of identifying, containing, and preventing outbreaks have been the foundation of public health for over 100 years. However, the growth of global travel challenges traditional interventions --pathogens do not respect borders. The rapid spread of SARS-CoV-2 and the resulting COVID-19 pandemic demonstrate this dramatically, but the current pandemic is not the only recent example.
When dozens of people were sick with Ebola Virus Disease (EVD) in rural southeast Guinea in West Africa in March 2014, physicians and other experts from around the world converged both to care for people in the outbreak regions and to contain the often-lethal disease before it spread to other countries or continents. By July 2014, the outbreak spread to Liberia and Sierra Leone and was detected in the capitals of all three countries. This was the first time Ebola had spread to urban population centers, raising the risk of international spread.
The response to the 2014 Ebola outbreaks was limited both by the poor public health infrastructure in the outbreak areas and the lack of effective medical countermeasures. In 2014, the world had only limited diagnostic tests for Ebola, and vaccines and therapeutics had not yet reached clinical trials.
By the time the outbreaks were halted in June 2016, at least 11,325 people had died, mostly in Guinea, Liberia, and Sierra Leone. Only 36 cases and 15 deaths had occurred in other countries, indicating successful containment, but the risk of new outbreaks and a global emergency remained high. While hundreds of heroic healthcare workers cared for people during the outbreak and helped contain it, others put their energy into a global effort to develop medical countermeasures:
Working with colleagues from across the U.S. government and the global public health community, the Ebola Medical Countermeasures Task Force at BARDA oversaw the research and development of therapeutics, vaccines, and diagnostic tests. The effort began in earnest within weeks of the initial outbreak in 2014, with the rapid progression of nonclinical studies and manufacturing scale-up to support clinical evaluation of the most promising Ebola therapeutic at the time, the ZMapp monoclonal antibody (mAb) cocktail developed by Mapp Biopharmaceutical. In parallel, BARDA partnered with Regeneron Pharmaceuticals to leverage Regeneron’s rapid antibody identification platform to develop another candidate mAb-based cocktail.
Similarly, BARDA ramped up investments in vaccines, supporting four different candidates that quickly progressed to clinical development. BARDA emphasized clinical development and manufacturing activities to ensure that we had safe and immunogenic candidates and that we had sufficient amounts of vaccines to conduct clinical trials. This resulted in three of the four candidates progressing into phase 2 or phase 3 clinical studies in Africa by 2015.
In parallel with BARDA’s investments in therapeutics and vaccines, BARDA also invested in the development of rapid diagnostics for fast confirmation of Ebola Virus infection to inform safe and dignified burial practices. This was one of the most significant interventions to reduce Ebola transmission because traditional funerals were “super spreader” events during Ebola outbreaks. The Ebola virus can be transmitted to other people from close contact with the body of an individual who died from Ebola, so quickly determining whether a death was caused by Ebola is essential. In response to the Ebola epidemics and to protect the U.S. and global community, BARDA invested in the development of a rapid point-of-care test, developed in partnership with OraSure Technologies, Inc. Authorized for emergency use by the FDA in 2015 and the World Health Organization in early 2016, this rapid diagnostic test uses oral fluids to determine whether a person’s body is infected, giving responders the information they need to make more effective decisions in the field. As a result of this collaboration, the OraQuick Ebola Rapid Antigen Test became the first FDA diagnostic to receive 510(k) marketing approval for Ebola in October 2019, and has been made available for use in recent Ebola outbreaks.
BARDA’s task force included field work in Sierra Leone to devise appropriate storage and transport capability as well as to train local healthcare workers during the West Africa outbreak. BARDA also provided on-the-ground operational, clinical, data management, and other technical support to the STRIVE study, sponsored by the U.S. Centers for Disease Control and Prevention and the Sierra Leone College of Medicine and Allied Health Sciences. This study, which evaluated the safety and immune response of the experimental rVSVΔG-ZEBOV-GP Ebola vaccine (brand name Ervebo®) manufactured by Merck in over 8,000 healthcare and front-line workers, was the first interventional clinical trial ever conducted in Sierra Leone. After the outbreak was declared over, BARDA continued to supply therapeutics for local flare-ups such as the 2016 cluster of cases in N’Zerekore, Guinea, and supported compassionate use of therapeutics in its portfolio in the U.S., Sierra Leone, Liberia, Guinea, the Democratic Republic of Congo, and Uganda. BARDA staff conducted exercises in Sierra Leone to advance preparedness and worked alongside State Department, CDC, and NIH colleagues to coordinate across nations and non-government organizations involved in the Ebola response.
Vaccines can be used during Ebola outbreaks so that, on an individual basis, family members, caregivers, and other contacts of infected individuals may be protected. Vaccines also improve the overall public health response by slowing or stopping ongoing transmission.
As a result of the BARDA team’s work, there now are four FDA approved, cleared or licensed Ebola countermeasures – a rapid antigen test, a vaccine, and two treatments, and another vaccine authorized by European authorities.
BARDA supported the advanced development and regulatory approvals of these products and worked directly with clinical and other partners on methods to rapidly deploy these medical countermeasures to communities affected in recent outbreaks.
Three BARDA scientists who led the Ebola task force - David Boucher, Dan Wolfe, and John Lee - are among the finalists for this year’s “Service to America Medals” for their work developing and deploying effective countermeasures to Ebola. They credit more than three dozen other BARDA professionals who contributed to preparing for and responding to the threat of Ebola. That group includes members of BARDA’s clinical, regulatory, manufacturing, and contracting teams and project officers from BARDA’s divisions of CBRN Medical Countermeasures and Detection, Diagnostics, and Devices Infrastructure who came together in a matrixed fashion to build project coordination teams that provided-- and continue to provide -- industry leading expertise to all of BARDA’s development programs.
In addition to this unrivaled expertise in advanced development and approval of medical countermeasures against national security threats, BARDA provided more than $700 million in funding for development of Ebola countermeasures.
The combination of medical countermeasures enables healthcare responders to form a so-called “ring of protection” around Ebola patients and, in turn, reduce the spread of the disease while also treating patients so that their chances of recovery improve.
Vaccines, designed to spur an antibody response within 14 days of a single dose, are given to family or others who are near Ebola patients. The antiviral therapeutics also significantly reduce Ebola deaths.
“With unpredictable outbreaks, it’s critical to have a vaccine that acts quickly to protect that ring of contacts,” says Daniel Wolfe, BARDA’s CBRN vaccines branch chief.
“Those vaccines were administered to family and other people close to a confirmed Ebola patient, while therapeutics were used to treat those already infected," explains David Boucher, chief of BARDA’s antivirals and antitoxins branch.
ERVEBO, which originated as a project of the Public Health Agency of Canada's National Microbiology Laboratory, now is registered for use in eight African countries and is part of a global Ebola vaccine stockpile. BARDA provided funding and technical support for clinical trials, advanced development, and manufacturing of the vaccine starting in 2014 after Merck licensed the vaccine from NewLink Genetics Corporation. BARDA supported expansion of production in 2017, enabling Merck to supply vaccine for the response to both the 2018 and 2021 outbreaks.
The Johnson & Johnson vaccine, which was developed and manufactured with BARDA support that also began in 2014, uses some of the same technology as the company’s COVID-19 vaccine. Using a non-replicating adenovirus prime and a modified Ankara virus (MVA) boost, the vaccine regimen delivers a gene to the human immune system that prompts it to create antibodies and prevent infection. BARDA support included funding and technical advice for small scale manufacturing and phase 1 clinical development through the late-stage development of each of these countermeasures.
In addition to the scientific and financial support, BARDA’s expertise with complex logistics also has been instrumental in the Ebola response. For example, BARDA scientists worked with local officials on ways to deliver Ebola vaccines and therapeutics under tight temperature control to remote areas.
“These areas sometimes required a two-day drive from the nearest airport and often had unstable electrical power,” said Boucher. BARDA logisticians and scientists worked with other public health responders to devise innovative solutions and contingency planning.
Another aspect of the BARDA Ebola Task Force’s work is applying lessons from Ebola to other potential health threats. In a paper published in the journal Human Vaccines & Immunotherapeutics, BARDA scientists outlined steps necessary to develop vaccines against other strains of Ebola or related viruses.
“I don’t think I can stress enough how incredible it is to go from where we were in early 2014, having limited diagnostics and only preclinical stage vaccines and therapeutics for Ebola, to where we are today,” said BARDA Director Gary Disbrow. “We now have four FDA approved, cleared, or licensed BARDA-supported medical countermeasures to combat this horrific disease.”
The Task Force group includes members of BARDA’s clinical, regulatory, manufacturing, and contracting teams and project officers from BARDA’s Divisions of CBRN Medical Countermeasures and Detection, Diagnostics, and Devices Infrastructure who came together in a matrixed fashion to build project coordination teams that provided-- and continue to provide -- industry leading expertise to all of BARDA’s development programs.
Learn more about BARDA's work in science and the impact of our countermeasures.