Now, finally, three studies in West Africa may provide that answer.
The World Health Organization and several partners announced Thursday they will start testing the vaccine in Guinea in a trial designed to prove whether it is effective. The trial will begin Saturday.
Later this month, the U.S. Centers for Disease Control expects to launch a trial of the vaccine — now licensed to biotech company NewLink Genetics and pharmaceutical giant Merck — in Sierra Leone.
In Liberia, the U.S. National Institutes of Health has begun to test two experimental Ebola vaccines against a placebo in a large randomized controlled trial. The Liberian trial is studying the NewLink-Merck vaccine as well as one designed at the NIH that is being developed by GSK.
These important studies are commencing several months later than had been hoped, past the peak of the West African outbreak. That could make answering the question — Do either or both of these vaccines work? — difficult. Yet people who have been pushing for the development of Ebola vaccines think the work remains critical.
"Testing investigational medicines during an epidemic is incredibly challenging, but this approach gives us the best possible chance of finding a safe and effective vaccine in time to save lives during the current epidemic, and to help us prepare for future outbreaks," said Dr. Jeremy Farrah, director of Britain's Wellcome Trust, which is providing funding for the Guinea trial.
Merck's vice-president for medical affairs and policy said he's convinced at least one of the experimental Ebola vaccines will make it over the hurdles of the licensure process.
"I think the world needs an Ebola vaccine and a pathway to make vaccines against other strains of Ebola and other related viral hemorrhagic fevers," Dr. Mark Feinberg said in an interview.
"I don't have any doubts that we will get there. I can't say that that's our vaccine or another vaccine."
When plans for the trials were first discussed late last year, it appeared Liberia might provide the needed data.
The trial there is massive, designed to enlist 27,000 people. A third will get the GSK vaccine, a third the NewLink-Merck vaccine and the remainder a shot of saline solution. It's a classic design, aimed at generating clear evidence that will satisfy regulatory agencies like the U.S. Food and Drug Administration.
Last fall Liberia's outbreak surpassed that of its neighbours. It seemed highly likely that — if the underlying science was sound — one or both of the vaccines would be shown to prevent infection.
Today Liberia's Ebola treatment centres are empty. That's a cause for celebration, to be sure. But if no one is catching Ebola, it doesn't matter how well designed the clinical trial being conducted there is. It cannot prove the vaccines work.
More hope is focused on the research in Sierra Leone and Guinea, where Ebola infections are occurring at a steady rate. In the former, the CDC decided the best hope for an answer would come from concentrating on a single candidate.
"We are trying to optimize getting an efficacy measurement for one vaccine," explained Dr. Anne Schuchat, director of the CDC's national centre for immunization and respiratory diseases. "Adding two would make it even less likely that we'd be able to measure efficacy."
The CDC team selected the NewLink-Merck vaccine after a review of the data on both vaccines suggested the NewLink-Merck product is more likely to be effective with a single dose and offer longer protection than the GSK vaccine.
"With fewer cases and the possibility that the trial may need to go on longer, a durable response was important," she said.
The trial will focus on health-care workers and front-line workers such as ambulance drivers; 6,000 volunteers will be randomly assigned to be vaccinated immediately or five or six months down the road.
Two smaller studies will be nested inside the trial. The first will examine reactions to the vaccine. It is expected to be fairly "reactogenic," inducing fevers, muscle aches and flu-like symptoms. As well, blood samples from a group of vaccine recipients will be studied to see what kind of immune response the inoculation provokes. Those studies will involve several hundred people each, Schuchat said.
The trial in Guinea will use an approach known as ring vaccination. When a new case is identified, his or her contacts will be randomly selected to be either offered vaccine immediately or after a three-week delay.
If the vaccine works, you would expect to see fewer secondary cases within the ring of quickly vaccinated contacts than among the case contacts who were not immediately vaccinated.
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