A new study has shown that people vaccinated against Ebola who still developed the disease had a substantially lower risk of dying than people who were not vaccinated, even if they received the vaccine when they were already infected with the virus.
It confirms just how major an advancement the Ebola vaccine remains; the study is the first to show that in addition to preventing infections, the vaccine can save some people who are already sick with the often fatal disease.
The research, based on data from the massive 2018-2020 Ebola Zaire outbreak in the Democratic Republic of the Congo, showed that the risk of dying of Ebola was halved among people who had been vaccinated with a single dose of Merck’s Ervebo before developing symptoms — including those who had only received the vaccine a day or two before becoming ill. While that is not enough time for the immune system to develop a robust response to a vaccine, there was clearly a benefit. The case fatality among people who had been vaccinated two or fewer days prior to becoming ill was 27%, compared to 56% among people who were unvaccinated.
“That’s a huge finding,” said Rebecca Coulborn, first author of the paper, which was published online in the journal Lancet Infectious Diseases late last week. “We know now that vaccination is better late than never. So this is one more reason to use the Ebola vaccine.”
Coulborn is an epidemiologist with Epicentre, a Paris-based division of Doctors Without Borders, which is known by the acronym from its name in French, MSF. She was part of a team of researchers from MSF and DRC’s National Institute for Biomedical Research that published the study, analyzing data from 2,279 confirmed Ebola patients from the 2018-2020 outbreak in northeastern DRC.
The scientists who developed this vaccine have long thought it could be used in a post-exposure setting, to improve the survival odds of people who have already contracted the disease. That belief was based on work done in animals — mice, guinea pigs, and non-human primates — and published in 2007 in the journal PLOS Pathogens.
In 2009, a German researcher pricked her finger with a syringe containing Ebola viruses, and was given the then-unlicensed vaccine in a bid to help her survive. She developed a fever — which could have been triggered by the disease or by the vaccine — but no other symptoms. It was never clear if she was infected or if the vaccine cut short her infection.
Still, before the development of effective antibody therapies for Ebola Zaire, this vaccine was considered the best hope for anyone exposed to Ebola. The various types of ebolaviruses, which belong to the filovirus family, have a case fatality rate of upward of 50%.
“Basically all of the filovirus researchers were saying, ‘Man, if I ever have an accidental exposure to filovirus, I’m very quickly going to have an accidental exposure to the vaccine,’” Armand Sprecher, an MSF physician who has been involved in Ebola outbreak responses dating back to 2000, told STAT. Sprecher was not an author of this paper.
Paradoxically, a recent attempt to replicate in primates the earlier findings of post-exposure benefit of the vaccine failed. Heinz Feldmann — who led development of Ervebo — and colleagues at the National Institutes of Health’s Rocky Mountain Laboratories in Hamilton, Mont., showed that macaques that were vaccinated after being injected with a lethal dose of Ebola had a slower progression of disease, but there was no survival advantage over control animals that didn’t receive the vaccine.
A paper reporting those results was published last July in the Journal of Infectious Diseases. It is not clear why that study failed to show that the vaccine was protective when given in a post-exposure setting.
But the concerns that research raised will be assuaged by the new study, the first to show a benefit of post-exposure use of the vaccine in people.
In the DRC outbreak, the Ministry of Health agreed to collect standardized data on suspected and confirmed cases at all Ebola treatment centers using a tool called a line list that Epicentre had developed. This outbreak was the first time the tool was used. While some of the entries were incomplete — vaccination status was missing from the entries of 841 of 2,279 confirmed cases used in the analysis — there is sufficient data to mine to look at questions like this one.
Coulborn and her co-authors compared the fatality rates of people who had been vaccinated to those who were known to be unvaccinated. Overall, the fatality rate among the vaccinated patients was 25%.
The longer it had been since an Ebola patient had been vaccinated, the better their chances of surviving. For people who had been vaccinated three to nine days before developing symptoms, the fatality rate was 20%; for those vaccinated 10 or more days before symptom onset it was 18%. The incubation period for Ebola runs from two to 21 days, meaning that anyone who developed symptoms in the three weeks after being vaccinated may have already been infected when they received the vaccine.
It’s believed that it takes about 10 days for the immune system to mount a robust response to this vaccine, so it would not have been surprising if there had been no survival advantage seen in people who developed symptoms in nine or fewer days since vaccination. That a benefit was shown among people who had been vaccinated two or fewer days before symptom onset suggests that before triggering the development of Ebola-specific antibodies, the vaccine may activate the innate immune response — the body’s first line of defense against invading pathogens. Ebola dampens the innate immune response; the vaccine may override that effect, Sprecher said.
Analysis of the data also revealed that people who had been vaccinated were less viremic — they had significantly lower levels of virus in their bodies. That could have helped those patients survive, the study suggested. In an interview, Coulborn said lower levels of virus in infected people could also help in the containment of Ebola outbreaks, potentially cutting the rate at which transmission occurs.
Another interesting finding of the study was that people who developed Ebola after having been vaccinated were treated as effectively with Ebola antibody products as people who had not been vaccinated. There was a theoretical concern that there might be some interference between the antibodies being developed in response to vaccination and the treatments used to try to cure the disease.
“Our results suggest no antagonistic effect between the vaccine and monoclonal antibody treatment, even when it is administered within a short interval,” the study noted.
That will give people working to quell Ebola outbreaks confidence that the vaccine can be given to people who have been exposed to an Ebola patient without risking their chances of responding to the antibody treatments, should they go on to develop symptoms themselves.
“The nice thing is, as they pointed out, that this is not in competition with the therapeutics,” Sprecher said. “So vaccine plus therapeutic is even better than either alone.”
Feldmann, who was not involved in the new study, admitted he was excited by the findings. “I think it’s very good. I don’t want to say, ‘Yes, we told you before,’ but it’s of course very assuring,” he said.