TORONTO – Canadian researchers are reporting a potential advance in the treatment of Ebola virus infection, one of the most deadly pathogens known to humankind.
Researchers from the National Microbiology Laboratory in Winnipeg are reporting that monkeys deliberately infected with Ebola were successfully saved with a cocktail of antibodies against the virus.
Four of four monkeys given the treatment 24 hours after infection survived. And two of four monkeys treated 48 hours after infection also survived.
There currently is no vaccine and no treatment for Ebola, a viral hemorrhagic fever that causes sporadic, tragic outbreaks in countries in central Africa.
This treatment isn’t ready for human use yet. And even if the work continues to look promising, hurdles will undoubtedly arise when attempts are made to translate findings in the lab to a usable therapy in the field.
Still, these results are creating optimism that a tool with which to combat Ebola outbreaks may be on the horizon.
“Our researchers have seen first hand the terrible effects of the Ebola virus on populations in Africa,” Dr. Frank Plummer, scientific director of the Winnipeg lab and chief science officer at the Public Health Agency of Canada, said in a news release.
“This discovery should pave the way for the development of a new drug that has the potential to save many lives.”
Plummer’s enthusiasm was echoed by Dr. Pierre Formenty, team leader for epidemic and emerging diseases at the World Health Organization.
“It’s excellent science,” Formenty said in an interview from Geneva. “And it’s very hopeful for us.”
Formenty says this work makes him more optimistic than he’s felt in years that a usable tool against Ebola may be in sight.
The paper is published in this week’s issue of the journal Science Translational Medicine.
Senior author Gary Kobinger said the goal is to get a treatment that works 72 hours after exposure, because in an outbreak situation one generally can’t be sure someone is infected until about three days after exposure.
Kobinger is the head of the special pathogens program at the Winnipeg lab, which is part of the Public Health Agency of Canada.
The work involved infecting macaque monkeys with Ebola Zaire, the deadliest species of Ebola viruses. In outbreaks triggered by the Zaire strain of Ebola, as many as 90 per cent of people infected may die.
The monkeys were treated with a combination of three monoclonal antibodies, specific antibodies against the protein on the outside of the Ebola virus that are isolated and cloned.
Previous efforts to treat Ebola with monoclonal antibodies — a single antibody or a pair of antibodies — had limited success.
Kobinger’s team identified eight monoclonal antibodies that might work, but homed in on three to try to reduce the cost of producing the treatment. Monoclonal antibodies are typically difficult and expensive to generate.
“We thought that the combination of three would be viable and that we would get a lot of efficacy out of three. But it was a little bit of guestimating at that moment,” he admits.
This cocktail would only counter Ebola Zaire. If this type of therapy is approved for use, different antibody combinations would be needed to treat people infected with one of the other types of Ebola. (There are five species of Ebola viruses, one of which — Ebola Reston — infects animals but hasn’t been known to trigger human disease.)
It’s possible that a super cocktail — one targeting several species of Ebola — might be concocted. Doses of the treatment or treatments might then be made and stockpiled for use when outbreaks emerge.
Kobinger said the antibodies have a long shelf life — which would be important for a therapy that might only be needed once every few of years. If stored at the right temperatures, the antibodies can last at least 10 years, he said. They can also be dried and stored at room temperature and later reconstituted.
Other experts in the small circle of scientists who do this type of work were encouraged by Kobinger’s findings. But at least one warned there are logistical and financial challenges ahead.
“It’s hard to make the amount of antibodies needed for several treatments as well as for larger groups of animals. So this is one of the biggest problems, I would think, is to produce these antibodies to quantities that can be used then in humans,” said Dr. Heinz Feldmann, who ran the special pathogens program in Winnipeg before Kobinger.
Feldmann is now chief scientist for BSL 4 laboratories — the highest level of biosecurity and biosafety — at the U.S. National Institute of Health’s Rocky Mountain Laboratories in Hamilton, Mont.
Producing and using a vaccine would be easier than going the monoclonal antibody route, said Feldmann, who works on both types of treatment responses for Ebola and the sister virus that causes Marburg fever. But monoclonal antibodies might be safer.
“There’s always pluses and minuses. This is certainly a very safe approach, unless you get some allergic reaction in an individual. But it will be a little bit more challenging and cost-intense to produce.”
Kobinger said talks are underway with a Canadian company about the possibility of producing the antibodies in plants, which would speed production and lower costs. (They are currently produced in mice.) But he acknowledged challenges remain.
“The only thing we have right now is a very good candidate for (Ebola) Zaire. But there is still lots of work to be done before we get there.”