As Canada prepares to ship out as many as 1,000 doses of an experimental Ebola vaccine, it is also preparing to hand off to international medical experts the gut-wrenching decisions about who in West Africa will receive an injection that could protect against the deadly virus – or cause unanticipated and dangerous side effects.
Canada is the first country to offer a potential treatment or vaccine that could be distributed on a wide scale in a region ravaged by the worst Ebola outbreak in history, putting this country’s research at the centre of a larger worldwide scramble to make available Ebola drugs that have, until now, been tested almost exclusively on animals and produced only in tiny batches.
“There’s a lot of challenges going forward with this,” said Gary Kobinger, the chief of special pathogens at Winnipeg’s National Microbiology Laboratory and the scientist who led the development of the vaccine. “I think this [releasing the vaccine] was a very important step and a crucial step to establish the foundation of a possible use.”
Dr. Kobinger and his colleagues at the Winnipeg lab also developed two of the three mono-clonol antibodies that form the basis of an experimental Ebola treatment known as ZMapp, which received widespread scrutiny after limited doses were offered to two U.S. health-care workers and a Spanish priest, but not to Africans.
Doctors Without Borders confirmed on Wednesday that in late July, its team in Sierra Leone agonized over whether to offer a single available dose of an untested treatment – believed to be ZMapp – to a top local doctor who later died of the virus.
That single dose was brought to Sierra Leone by a team from the Winnipeg lab, the aid organization said, with the intention of testing it for heat-sensitivity, not injecting it into an ill patient.
The dilemma Doctors Without Borders faced in that case highlights a larger ethical conundrum.
Broadly, the Ebola treatments would be tested on non-human subjects first to see how effective they are. After successful completion of that stage, they could be tested on human subjects who do not have Ebola. That kind of testing helps determine correct dosage, and whether the treatment has unintended side-effects.
But the best way to test the effectiveness of a treatment is to conduct a double-blind, placebo-controlled study with a large sample of patients. The current outbreak, which is the biggest in history, offers exactly what is needed. In other words, the tragic magnitude of the outbreak may ultimately provide the conditions for the eventual eradication of the virus.
“The one thing you need for this kind of trial is a hospital full of patients,” said Erica Ollmann Saphire, a professor with the California-based Scripps Research Institute and an expert on viral hemorrhagic fever pathogenesis.
“Well, now they got it, sadly.”
Dr. Kobinger’s own change of heart underscores the ethical conundrum surrounding untested therapies or vaccines for Ebola.
Shortly after he and two other scientists from the Winnipeg lab returned from Ebola-related work in Sierra Leone last month, Dr. Kobinger told the Canadian Press it would be too risky to use experimental tools to combat the outbreak.
“These are all experimental drugs that have not met the requirements … even for a Phase 1 [trial] right now in humans. So they have to pass all the toxicity [tests], they have to pass the safety trials,” he said in late July.
But, since then, the outbreak has spread, claiming more lives – 1,975 people have been infected and 1,069 have died as of Aug.11, the World Health Organization said on Wednesday – and ethics panels convened by Canada and WHO have given the green light to experimental options, provided patients consent and the results are shared.
Not long after the WHO panel announced its support for the experimental route on Tuesday, Health Minister Rona Ambrose called Margaret Chan, the director-general of WHO, to offer the Canadian vaccine, about 1,500 doses of which are in storage in Winnipeg.
The batch was made in Germany, Dr. Kobinger said. Although Canada has retained the intellectual property rights to the vaccine, it has licensed an Iowa-based company, NewLink Genetics Corp., to produce it for human trials.
Last week, the company’s wholly owned subsidiary, BioProtection Systems Corp., received $1-million (U.S.) from the United States Defense Threat Reduction Agency (DTRA) for more preclinical toxicology studies, including stepped-up manufacturing, to allow human trials to begin quickly.
The VSV-EBOV vaccine could be used in two ways, Dr. Kobinger said. It could be administered in low doses to people who have not been infected and in high doses to those who have already contracted it, provided the infection is caught early.
“It can have action on both sides, a little bit like the rabies vaccine that can be given after having been exposed to rabies,” he said.
A spokesman for WHO said the agency has not yet determined when, where or to whom the vaccines will be offered.
“This is not a political decision at all,” Shelly Glover, the Canadian Heritage Minister, said Wednesday at a news conference, explaining why Canada decided to release the vaccine. “This is a very serious disease that has taken the lives of many, many people and we’re working hard as a country to provide assistance to the global community. This is a decision that will made by experts and not politicians.”
With reports from Reuters and Canadian Press