TORONTO -- The first human trials of a designed-in-Canada Ebola vaccine suggest it is safe and triggers a rapid immune response, two articles published Wednesday reveal.
The work, based on six clinical trials in the United States, Switzerland, Germany, Gabon and Kenya, found the vaccine quickly generates antibodies in people who receive it. Whether those antibodies protect against infection remains to be seen, but early evidence suggests that is a strong possibility.
The vaccine is called rVSV-ZEBOV and was created by scientists at the National Microbiology Laboratory in Winnipeg, part of the Public Health Agency of Canada. It is being developed by U.S. biotech NewLink Genetics and pharma giant Merck.
Published in the New England Journal of Medicine, the articles describe Phase 1 clinical trials which represent the first time this vaccine was given to a number of people. The two U.S. trials are reported in one article while the other presents findings from the European and African research.
Phase 1 trials are designed to show if an experimental product is safe and to help determine what an appropriate dose should be. They are too small to answer the question: Does this vaccine work?
It is hoped the answer will come from larger Phase 3 trials currently underway in West Africa.
Volunteers who were vaccinated started to generate antibodies quickly. That is an attractive feature in a vaccine that would be used to quell future Ebola outbreaks, if it makes it through the licensing process.
"There were pretty positive signals of immunogenicity at 14 days post vaccination across both of the (vaccine) doses that are reported," said Col. Stephen Thomas, a senior author of the article describing the two U.S. trials. Those trials were conducted at the Walter Reed Army Institute of Research and the U.S. National Institute of Allergy and Infectious Diseases, both located in Bethesda, Md.
By Day 28, all the vaccinated volunteers had shown an antibody response. A total of 190 participants received the vaccine in the six studies combined.
The article reporting on data from the European and African trials revealed that blood from vaccinated subjects contained neutralizing antibodies -- the type that can kill Ebola viruses. This finding adds weight to the belief that the vaccine should protect against infection.
The vaccine was fairly reactogenic, which means it induced side-effects in many of the people who received. They included fever, muscle aches and even arthritis-like joint pain on occasion. In fact, the trial in Geneva, Switzerland was temporarily halted before Christmas when the arthritis-like reaction was seen. It had not been expected.
That side-effect hasn't been reported by other groups testing this vaccine, though it was experienced by two of 40 participants in Germany and Kenya. A couple of the people who reported joint pain experienced it for weeks, but in most cases it went away more rapidly.
In fact, the side-effect profile of the vaccine was considered to be acceptable, especially given the lethality of the disease the vaccine aims to protect against.
The combined work also points to a pattern of side-effect timing that may relieve some experts who had worried about using the vaccine in a setting where Ebola viruses actually circulate. They have been concerned that a vaccine that induces fever might make it more difficult to detect Ebola infections early, given that fever is often the first sign of disease. Early detection and isolation of infected people are key tools in Ebola containment efforts.
The research teams found that fevers, when they occurred, happened early and resolved quickly. That should make it easier for people running the trials in West Africa to distinguish vaccine-triggered fevers from Ebola-induced ones, suggested Dr. Claire-Anne Siegrist, the principle investigator for the European and African trials.
"You tell people, 'Look, if you have fever tomorrow, this is the vaccine. But if it lasts for more than two days, you come and see us immediately.' That's quite easy," said Siegrist, director of the Centre of Vaccinology of the University Hospitals of Geneva.
