Human safety tests on a promising experimental Ebola vaccine were halted temporarily when some subjects experienced arthritis or joint pain for a period of roughly a week to several months, according to researchers.

The drug, VSV-ZEBOV, is one of two top candidate vaccines that were rushed into testing at the height of the Ebola epidemic in West Africa.

The vaccine uses a genetically modified livestock virus to trigger the production of Ebola virus antibodies, and was deemed safe in Phase 1 trials conducted on 52 volunteers in the United States, according to research published recently in the New England Journal of Medicine.

However, another set of Phase 1 trials conducted on 158 participants in Europe and Africa surprised researchers when 22% of test subjects in Geneva experienced arthritis and joint pain more than a week after being injected with the vaccine.


Researchers responded by suspending the Geneva trial for a month. The tests resumed on Jan. 4, but vaccine dosages were reduced, according to Dr. Claire-Anne Siegrist, a professor of vaccinology at the University of Geneva, and the senior author of a preliminary report on the trial.

The single-dose vaccine should be further evaluated for safety and efficacy, Siegrist and her colleagues concluded.

The vaccine was developed by the Canadian National Microbiology Laboratory and licensed to a subsidiary of NewLink Genetics. The vaccine was subsequently licensed to Merck, which has assumed responsibility for ongoing research and development.

It remains unclear exactly why participants in the double-blind randomized placebo-controlled trial in Geneva suffered such adverse side effects when trial volunteers in other locations did not.


Eleven of 51 study participants experienced joint pain, although none had a history of such problems.

“Arthritis was confirmed in 9 of 11 participants,” study authors wrote. “Pain was often migratory and generally mild, with a median duration of 8 days, but lasting more than 3 months in 1 participant.”

The Geneva trial involved larger doses of the vaccine than other locations. This means that some study participants received greater quantities of the weakened and modified vesicular stomatitis virus, and their bodies may have taken longer to clear the virus from their systems.

“It is reasonable to assume that viral clearance was not as rapid/effective in subjects with arthritis,” Siegrist wrote in an email to The Times. “However, the hypothesis of a dose effect is yet only a hypothesis: it could also be intrinsic viral properties. We are currently ascertaining this.”


Researchers have already developed two new versions of the vaccine that use an even more “crippled” version of the virus, but provoke the same immune response as the original vaccine, according to Thomas Geisbert, a professor of microbiology at the University of Texas Medical Branch at Galveston.

In a paper published Tuesday in the journal Nature, researchers at UTMB Galveston and Profectus BioSciences Inc., said they began developing the new vaccines after learning of the Geneva trials -- as well as instances of “robust post-vaccination viremia” in lab monkeys.

“I am not sure we fully understand what happened in Geneva,” Geisbert wrote in an email to The Times.

“We knew that there would be safety concerns when the first generation of VSV-based Ebola vaccine was developed. We did everything that we could to address those concerns ... The next logical step in that process was to see if we could find a VSV vector that was even safer/more attenuated without compromising immunogenicity and safety.”


The new vaccines were administered to eight of 10 macaques which were then exposed to the Makona variant of Ebola -- the West African variant that is responsible for more than 10,572 deaths. (The variant is named after a river that runs through or borders the three worst hit nations: Liberia, Guinea and Sierra Leone.)

All eight monkeys who were given the vaccine survived. The two monkeys who did not receive the vaccine died, researchers said.

When the blood of the surviving monkeys was examined, VSV levels were 10- to 50-fold lower than monkeys who were given the original vaccine, authors wrote.

“In a well ordered universe, this would suggest that we would see fewer and less severe adverse events in humans,” Geisbert said.


Researchers hope to test the new vaccines on humans in Phase 1 trials this summer.

Geisbert has championed the use of a VSV-based vaccine because it can be administered as a single dose. The other top vaccine contender, which was developed by the National Institute of Allergy and Infectious Diseases and the pharmaceutical firm GlaxoSmithKline requires a booster shot after six months.

A single-shot vaccine could be widely administered to people in Ebola endemic regions to provide “blanket immunity,” researchers say.

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