Used in Trial of 27,000 West Africans
By Annette M. Boyle
WASHINGTON — When dozens of patients suffering with fever, severe diarrhea, hemorrhage and vomiting started dying in Guinea in early 2014, physicians and researchers suspected they were seeing the first major outbreak of Ebola in West Africa. Tests from a biosafety laboratory confirmed the disease but could not identify the strain.
At that point, the idea an Ebola vaccine would be ready for trials in a matter of months was far-fetched, at best. Yet, just more than a year later, a study was published in a major journal reporting that a candidate vaccine had been found to be safe and to generate the necessary immune response. It already is being tested in a trial of 27,000 healthcare workers and others in West Africa.
A large share of the credit goes to the DoD’s Joint Project Manager Medical Countermeasure Systems (JPM-MCS), which had developed the assays now considered a gold standard for Ebola detection and then played a key role in expediting vaccine research.
For the past 12 years, MCS and its three predecessor organizations have focused on developing a full range of medical countermeasures. “In my world, that’s a vaccine or a diagnostic test to see what someone been exposed to, and therapeutics to treat them,” said Col. Russell E. Coleman, PhD, Joint Project Manager, Medical Countermeasure Systems.
In 2007, the group recognized the potential for the shattering impact of deliberate misuse of the Ebola virus, noting the risk of “significant potential for mass casualties or devastating effects to the economy, critical infrastructure or public confidence.”
When Ebola emerged in West Africa last year, MCS had a number of programs in process to detect, treat and protect against it but had to redirect efforts to respond to the developing humanitarian crisis. It also partnered with numerous other governmental agencies to test and gain rapid approval for critical tools in the fight against the hemorrhagic disease.
“In contrast to cancer, there’s not a population in the U.S. where we can go into a hospital and test the Ebola vaccine or a therapeutic agent,” Coleman told U.S. Medicine. “And, generally, Ebola flares up and lasts just a month or two, so it hasn’t been feasible to test drugs in people.”
With the West African outbreak, thousands of patients became ill in multiple countries, increasing international concern about a pandemic. Against this backdrop, the DOD, Department of Health and Human Services and Food and Drug Administration worked together to provide resources valuable in the outbreak.
Preventing Future Outbreaks
While containing the outbreak was crucial, the need to prevent future viral outbreaks also became urgent.
MCS had conducted animal testing on some components of a trivalent vaccine targeting three filoviruses: Ebola Zaire, Ebola Sudan and Marburg. In conjunction with the Walter Reed Army Institute of Research (WRAIR), the National Institute of Allergy and Infectious Diseases and other resources, MCS was able to accelerate testing of a vaccine specifically for the West African outbreak of the Ebola Zaire strain.
“Medical Countermeasures approached WRAIR about further developing and testing an Ebola vaccine, and we were enthusiastic and willing to be part of that,” said Col. Stephen Thomas, MD, WRAIR’s deputy commander.
The government agencies and vaccine manufacturers NewLink and Merck looked at three doses of the candidate vaccine, VSV-EBOV, which was initially developed by scientists at the Public Health Agency of Canada’s Microbiology Laboratory. The dosages were tested in four groups of 10 volunteers with three controls in each group receiving a placebo. The 39 study participants at Walter Reed received a single injection, while the 13 at the National Institute of Allergy and Infectious Diseases received two.
“The vaccine was found to be safe and to generate the immune response we were interested in,” said Thomas. Within two weeks of a single dose vaccination, 93% of volunteers had Ebola antibodies. By day 28, all volunteers showed Ebola glycoprotein antibody response. Results of the trials were published in April by the New England Journal of Medicine. 1
Data from the WRAIR vaccine trial helped scientists determine the appropriate vaccine dosage for ongoing mass immunization in Liberia, Guinea and Sierra Leone.
“As an agile organization, we were able to develop assays for Ebola by setting aside work on HIV and could redirect people to work on clinical infectious disease trials and other programs. Everyone devoted 100% of their time and focus to this problem to respond as quickly as possible,” Thomas told U.S. Medicine.
The Ebola crisis necessitated a rapid response from military organizations and other governmental agencies, although some critics have questioned whether necessary safety steps were jettisoned to speed the process.
To facilitate the approval of assays, vaccines and therapeutics, “we looked at some steps in parallel rather than sequentially. The FDA and other agencies were involved on a daily basis, and every one of the ethical and regulatory boxes that needed to be checked was checked, with everyone devoting 100% of their time and focus to this problem,” Thomas said.
Coleman echoed the point. “In the military, we know that myriad of threats could pop up at any time anywhere. It would take $5-$6 million to get FDA approval for every assay we have in development, so we have prepositioned emergency-use authorizations that allow us to proceed quickly in a declared emergency. It took just 30 days to turn around the pre-diagnostic packet for Ebola and have an assay that could be legally used in the U.S.”
Therapeutic agents received the same expedited treatment. “We had three products in development for Ebola virus, but none were ready to be licensed. The FDA allows emergency INDs [investigational new drug filing], which enabled us to work with Tekmira to provide therapeutics to non-DOD personnel. We did the same with the MediVector product, which is now completing clinical III trials,” he noted. The two drugs have been used in 13 patients who were evacuated to the U.S. or Europe.
“Infectious diseases are a constant threat to the U.S. DoD and to national security. Today, people can get from one place to another across the world in 24 hours very easily,” Thomas pointed out. Programs like Medical Countermeasures and institutions such as Walter Reed show the value of agility and preparation in addressing acute mission needs and global threats to health.
1 JA Regules, et al. A recombinant vesicular stomatitis virus Ebola vaccine — preliminary report. New England Journal of Medicine, April 1, 2015.