It took a major Ebola epidemic that led to more than 11,000 deaths, but we now finally have a successful Ebola vaccine candidate in development. If approved, the vaccine would vastly reduce the likelihood of ever seeing another major Ebola outbreak.
More than a year ago, researchers published striking preliminary results from a large trial on a vaccine called rVSV-ZEBOV in the Lancet. They showed that everyone who got the shot immediately after contact with an Ebola victim didn't get the virus.
Today, the same researchers — who hail from the World Health Organization, Guinea’s Ministry of Health, Public Health England, and other international partners — have unveiled their final results in the Lancet, and they’re just as remarkable. The vaccine was tested in a trial involving nearly 12,000 people in Guinea and Sierra Leone during 2015 and 2016. Among the 5,837 people who got the vaccine, no Ebola cases were recorded. By comparison, there were 23 Ebola cases in the control group that had not gotten the vaccine.
"This trial, confirming the 100 percent efficacy of the rVSV Ebola vaccine, is a simply remarkable outcome," Dr. Jeremy Farrar, the director of the Wellcome Trust, said of the research. "We’ve shown that by working collaboratively, across international borders and sectors, we can develop and test vaccines rapidly and use them to help bring epidemics to an end."
One of the most fascinating things about the vaccine — beyond its apparent safety and effectiveness — is how the researchers studied it.
When they launched the trial in 2015, the number of Ebola cases in Guinea had already declined, and there were too few cases to run a meaningful traditional randomized study (giving the vaccine to a randomly selected group and comparing it with a control group that doesn’t get the vaccine). So the researchers had to be creative. They decided to try something called "ring vaccination," a public health method used to eradicate smallpox in the 1970s. It involves immunizing the immediate contacts — friends, family, housemates, neighbors — of a person who falls ill with a virus to create a protective ring around them to stop transmission.
As soon as a new Ebola case was diagnosed, the researchers traced all their contacts for a total of 117 clusters (or "rings"), each made up of about 80 people. They then randomized the rings of people to get the vaccine either right after their friend or family member had been diagnosed or after a three-week delay.
Their preliminary results were so positive that the researchers changed the trial design so that everyone got the vaccine immediately, including children. A little more than half of those vaccinated (3,149 people) reported at least one side effect, but they were mostly mild (headache, fatigue, and muscle pain). Eighty serious adverse events were reported, but only two (a fever and an allergic reaction) were deemed to be related to the vaccine. "Adverse events data indicated no safety concerns in adults or children," the researchers concluded.
These results build on studies in non-human primates, which showed the vaccine was safe and completely protected them from Ebola.
Researchers are calling this development one of the only positive outcomes of the 2014-2016 Ebola epidemic — the largest the world had ever seen.
"The Ebola vaccine studies during the Ebola outbreak were one of the few successes of the collective international response," said John-Arne Røttingen, director of the division of infectious disease control at the Norwegian Institute of Public Heath, who worked on the study. "The world managed to plan and conduct more than 15 clinical trials in less than an year. And this ring vaccination trial, with its innovative research design, managed to demonstrate efficacy for one of the vaccines."
The vaccine was discovered by the Public Health Agency of Canada and is now under development by the drug company Merck. For now, Merck is doing additional safety studies on children and other vulnerable populations and will be seeking approval from a regulator like the US Food and Drug Administration by the end of next year. In case of an emergency, the company has committed to ensuring that 300,000 doses of the vaccine are available, so the vaccine won’t hit the market just yet.
And questions about the vaccine’s long-term effectiveness remain. "One question that has not been adequately addressed, even in nonclinical studies with any Ebola virus vaccine, is with regard to durability — is the vaccine long-lasting?" wrote Thomas Geisbert, an Ebola virus and vaccine expert from the University of Texas Medical Branch in Galveston, in an accompanying editorial. "Is it still protective, for example, 2–3 years after the vaccination?" Geisbert also wonders about whether the vaccine can be tweaked so that there are fewer side effects.
There’s also the question of how to speed up the development of vaccines for deadly viruses like Ebola, which may seem like distant threats — until it’s too late. The virus was discovered in 1976 but mainly affected people in Africa until the 2014 outbreak in West Africa, which affected more than 28,000 people and killed more than 11,000. The Department of Defense and other funders only started to pour money into Ebola vaccine development when the virus was deemed a biological weapon after the 9/11 terrorist attacks.
"Had a vaccine been available earlier in the Ebola epidemic, thousands of lives might have been saved," Farrar added. "We have to get ahead of the curve and make promising diagnostics, drugs, and vaccines for diseases we know could be a threat in the future." Farrar hopes this success story will inspire stakeholders to prepare for future potential epidemics — an important message at a time when the likelihood of global outbreaks is only accelerating.