The latest Ebola outbreak in the Democratic Republic of the Congo, which was only confirmed to be ongoing over the weekend, is already the fourth largest on record. The deadly virus is widespread in conflict zones, and the recent experience with Ebola shows it will be difficult to contain. There is no vaccine that targets the virus strain, Bundibugyo, which is prevalent there.
However, there is a small amount of scientific evidence to suggest that the existing licensed Ebola vaccine, Merck’s Ervevo, may provide some protection against the Zaire Ebola virus, a different strain of Ebola, even though it is designed to target this virus.
The World Health Organization and scientists who study these viruses are debating whether Elvebo could help contain this outbreak. A meeting of the expert group that advises the WHO on developing the necessary vaccines is scheduled for Tuesday, and the question of whether Elvevo should be put into trials will be on the agenda, Vathy Moorthy, acting leader of the WHO’s so-called Research and Development Blueprint Group, told STAT.
But ultimately, whether a vaccine is used in this outbreak will require requests from affected countries.
“Any decisions regarding next steps will be taken by the Democratic Republic of Congo and Uganda, with support from the WHO,” Moorthy said, adding that there are ethical and other considerations, including whether people from endemic areas will participate in clinical trials.
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The WHO on Sunday declared the rapidly spreading infectious disease outbreak a public health emergency of international concern. As of Monday, DRC had reported 395 suspected cases and 106 deaths, according to the Africa Centers for Disease Control and Prevention. Two cases were detected in Uganda, both of whom had traveled from the Democratic Republic of the Congo. One of them died.
Evidence that Elbebo may be cross-protective against Bundibugyo comes from a small study in primates. Opinions differ on how likely these results are to protect people and whether it is worth trying to see if there is any benefit.
“If you get it, it’s bad, but if you don’t cause it, it’s bad,” said virologist Darryl Falzarano, lead author of a 2011 paper published in the Journal of Infectious Diseases that showed some cross-protection of the vaccine in macaque monkeys.
“There’s very little data to support it, and we’re going to go almost blindly thinking it’s unlikely to get worse, but it’s possible,” said Falzarano, chief scientist at the University of Saskatchewan’s Vaccine and Infectious Disease Organization (VIDO).
There are several species of Ebola virus, four of which are known to infect humans. Of the four, Bundibugyo is the most recently discovered. Bundibugyo outbreaks have only been recorded twice in the past, in 2007 and 2012. Based on data from these two outbreaks, the virus is believed to be less lethal than the Zaire and Sudanese Ebola viruses, but with an estimated 50% fatality rate, it remains a dangerous threat.
Studies over the years suggest that the four Ebola species that infect humans are genetically distinct enough from each other that medical countermeasures developed for one will not protect against the others. So it was with some surprise that the group responsible for the 2011 paper found that macaques vaccinated with Ervebo’s precursor were more likely to survive than unvaccinated control animals when exposed to otherwise lethal doses of the virus.
In this study, three out of four vaccinated animals survived exposure to the virus compared to one out of three unvaccinated animals, but all vaccinated animals developed symptoms of the disease. (Primate research always uses as few animals as possible, both for humane reasons and because of the high cost of animals.)
Study author Tom Geisbert, an Ebola expert at the University of Texas Medical Branch, said the fact that one of the control animals survived despite not being vaccinated illustrates the difficulty in interpreting the results.
“If you have three out of four survivors, you have to take into account that some of those survivors might not have been vaccinated and survived,” he said, suggesting that fact probably means the protection is only around 50%, not 75% (if at all).
Geisbart said a larger study would have given him more confidence that the vaccine could be of great benefit in human use.
But other scientists see enough evidence to at least study whether the vaccine offers any protection against Bundibugyo, especially since the alternative is no vaccine.
“What’s the old Donald Rumsfeld line? You fight an outbreak with the vaccine you have, not the vaccine you wish you had or might someday have,” said Armand Sprecher, an emergency physician with Médecins Sans Frontières (MSF) who has responded to multiple Ebola outbreaks.
“The non-human primate studies are the rationale for saying, let’s use this vaccine, because we have it, we know it’s at least safe, the platform works, and the non-human primate data suggests it works,” he said. “We’ll use what we’ve got. We have the option of doing nothing, but I don’t think that’s acceptable.”
Merck, the maker of Elvevo, did not say whether it was willing to have Elvevo used in clinical trials during this outbreak.
“It is unknown whether Elvevo provides protection against other strains, including Bundibugyo. Some studies have been conducted independently from Merck to investigate the potential for cross-protection of other Zaire Ebola virus-containing vaccines against other Ebola virus strains, including Bundibugyo, but data are limited and not derived from human data or evaluation of Elvevo,” the spokesperson said in an email.
Some scientists are reportedly concerned about the idea of testing a vaccine against Bundibugyo, fearing it could backfire in some way.
There is some in vitro evidence that vaccines against one type of Ebola virus, when used to protect against another, can cause so-called antibody-induced enhancement, or worsening of the disease. However, its effectiveness has not been confirmed in animal experiments.
Falzarano said he’s not too worried about the disease, called ADE, but about the fact that administering a vaccine aimed at boosting the immune system to fight off the Zaire Ebola virus could distract vaccine recipients from their job of boosting their immune response to Bundibugyo if they encounter the virus.
But he suggested that if it could be installed, Elbevo could be used in well-run clinical trials in the region, despite the challenges it would no doubt face in isolated areas where conflict continues. Otherwise, he would consider using the vaccine “too risky.”
The decision will not be easy given the lack of data.
“To me, this is not a slam dunk,” Geisbert said.
