And while the Geneva-based trial of the rVSV-ZEBOV got back on track, researchers at Oxford University began testing another Ebola vaccine, made by the Janssen Pharmaceutical Companies of Johnson & Johnson.
The Janssen vaccine joins rVSV-ZEBOV, which is being developed by Merck and NewLink Genetics, and a vaccine being developed by GSK (formerly GlaxoSmithKline) in the race to provide the world with a licensed Ebola preventative.
The Swiss trial of rVSV-ZEBOV was temporarily suspended in mid-December after several participants reported experiencing pain in the joints of their fingers or toes about two weeks after being injected with the vaccine. It has been resuming using a substantially lower dose of the vaccine than what was given earlier.
A two-week Christmas break had been planned for the trial, but that hiatus — stretched to three — was started early so the research team could investigate the reaction.
At the time the trial was halted four participants had complained of experiencing joint pain. Dr. Angela Huttner, one of the researchers heading the trial, said more cases came to light, but she would not reveal how many of the 59 volunteers enrolled in the study before the break reported joint pain.
"The number did go up," she acknowledged in an interview Tuesday.
During the pause the researchers studied a number of the people who reported joint pain to see if they could find another explanation for the problem. But in the end they concluded the pain was likely a side-effect of the vaccine. The study's informed consent form was altered to warn future volunteers they might experience joint pain after vaccination.
"We did very extensive work-ups to rule out other causes, to rule out infections and any other kinds of things that can bring on these kinds of joint symptoms," Huttner said.
"We do feel that the joint symptoms were linked to the vaccine."
Most of the complaints related to pain in fingers and toes, but some people reported pain in their knees, she acknowledged. And while it had not been expected as a side-effect for this vaccine, Huttner and her colleagues pointed out that joint pain is a known side-effect of other live-virus vaccines.
(This vaccine, which was designed at the National Microbiology Laboratory in Winnipeg, is made with a live vesicular stomatitis virus that has been genetically altered to include a key Ebola protein. The VSV virus doesn't sicken humans — it is a virus that infects some animals — but it does deliver the Ebola protein to the immune system, which starts producing antibodies against Ebola as a result. It cannot cause Ebola disease.)
Vaccines that protect against rubella are also known to cause joint pain, in up to about 20 per cent of recipients. Huttner said the percentage of people who experienced joint pain in the Geneva study was not higher than 20 per cent and the symptoms have gone away in most cases.
"Almost all cases are resolved now. The intensity was fairly mild. There were some cases of ... pain that was reported to be moderate, not just mild. But all people were able to work. Nobody was hospitalized," she said.
"And yes, there are a couple of people who still have some ongoing pain, but it's very mild. And it's considered less than at the time of diagnosis. ... (It's) just taking a little while to diminish."
The trial, one of at least seven Phase 1 trials of rVSV-ZEBOV, is being conducted at the University Hospitals of Geneva. The researchers plan to enrol another 56 volunteers, giving some a placebo and others a low dose of the vaccine.
"We actually believe this could be very immunogenic, even at a lower dose. That's why we were willing to go down," Huttner said.
A Canadian trial of the vaccine is also being conducted, at the Canadian Centre for Vaccinology at Dalhousie University in Halifax. A spokesperson for the centre, Mary Appleton, said via email Tuesday that 40 volunteers — the targeted number — have been vaccinated in that trial, with no side-effects of concern noted.
The Canadian trial is testing three low doses of the vaccine.
Phase 1 trials are designed to show that a drug or vaccine is safe to use in people and to determine what the dose should be. Larger later-stage trials try to answer the question of whether an experimental product actually works.
Planning is underway to do those larger trials to test two vaccines — rVSV-ZEBOV and a vaccine designed at the U.S. National Institute of Allergy and Infectious Diseases called cAd3-ZEBOV — in Liberia, Sierra Leone and Guinea.
It has been hoped the trials could begin this month, though concern is rising that the falling rate of new Ebola cases in West Africa may make it difficult to show the vaccines actually work.
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