Three clinical trial volunteers sit next to Kirsten Lyke, a tropical disease researcher, as she discusses her work on the phone. All had come to the University of Maryland, in Baltimore, to receive a dose of an experimental Ebola vaccine. "We’re finishing up our last set of vaccinations today," she says. And "right around the new year, we will have the new data."
"We’re finishing up our last set of vaccinations today."
Monday was the last day of the University’s early-stage Ebola vaccine trial involving healthy participants. It's aimed at determining whether the vaccine is safe, tolerable, and effective at provoking an immune response. The vaccine, called "cAd3-EBOZ," is one of two Ebola vaccine candidates currently under human investigation in North America. The other vaccine, one that was developed by researchers at the Public Health Agency of Canada’s National Microbiology Laboratory, begins human trials in Halifax, Nova Scotia this week.
"These two vaccines are the farthest along that are in clinical trials," says Scott Halperin, a microbiologist at Dalhousie University and one of the researchers investigating the vaccine in Halifax. But right now, it’s hard to tell if either vaccine will make it to market. "Until you actually test vaccines in humans, you really don’t know which one will work."
Vaccines are at the forefront of research efforts to curb the Ebola outbreak in West Africa that has already claimed the lives of over 5,100 people. They’re the type of intervention that could help those who are most at risk — healthcare workers and citizens in Guinea, Liberia, and Sierra Leone — protect themselves against infection. Yet both Lyke and Halperin are quick to caution against putting all our eggs in the preventative basket. To stop the spread of Ebola, the world also needs to stick to the basics of infectious disease interventions. And researchers need to explore treatments for those already infected as well, like "convalescent whole blood" — a treatment that essentially means injecting people with the blood of Ebola survivors.
Survivor blood and drugs
The World Health Organization recently told scientists that they should the use the blood of Ebola survivors to treat others. The announcement was surprising to some because researchers have yet to conduct a large-scale clinical trial to look into its effectiveness.
"Based on what we know about science, it should work," Lyke says. Using antibodies contained in the blood of recovered patients is a well-established technique used for several infectious diseases. And several Ebola survivors, including physician Kent Brantly, have already donated their blood to help treat Ebola patients.
Transfusions from Ebola survivors "should work."
Without a clinical trial, however, it's hard to determine how useful the transfusions have been, so the Institute of Tropical Medicine in Belgium is planning a trial. "What we need now is a well-designed study according to high ethic and scientific standards to confirm it works," says Roeland Scholtalbers, head of communications at the Institute of Tropical Medicine in Belgium. In mid-December, the Institute will hold a trial in which 200 patients will receive blood or blood plasma from Ebola survivors. The trial will last about one year, but researchers hope to see results as early as March, which could inform a decision about possibly scaling up this intervention — or stopping the practice altogether.
If using the blood of survivors proves ineffective, there are a number of drug-based Ebola treatments that might yield some positive results. The anti-Ebola drug Zmapp has already been given to a number of Ebola patients, and Thomas Duncan, the first person diagnosed with Ebola in the US, was famously given the anti-viral brincidofovir before his death. Yet despite a favorable safety record, brincidofovir had only been tested against Ebola in petri dishes prior to being given to Ebola patients. And Zmapp — a drug that contains artificial antibodies — still hasn't undergone clinical testing, which means that we still don’t know if it's effective, or even safe. Moreover, Zmapp is in extremely short supply, so many researchers have moved past it. "We can’t really give it to people anyways," Lyke says, "until [the company that makes it] produces more."
Recipe for an Ebola vaccine
Without an effective drug candidate or treatment, prevention becomes more important. Informing the public about how to avoid becoming infected is essential, but a vaccine could help thousands of people avoid the disease without having to think too much about it.
The two candidates that are being tested on humans are based on the same principles as all vaccines are. Both make use of an virus that normally infects non-human animals. To make an Ebola vaccine, scientists first manipulated a virus and deleted one of its genes. Then, they inserted a gene from the Ebola virus into the animal virus, so the animal virus manufactures Ebola proteins that are harmless to humans. "So when the virus is given to people, and their bodies detect the Ebola protein on its surface, they make antibodies against that protein," Halperin says. A vaccinated individual would therefore already have the means to fight the virus off if they encountered Ebola in the environment.
healthy individuals have been more than willing to try the vaccine
Each vaccine uses a different "host" virus: The Canadian vaccine makes use of a virus that normally infects cows, whereas the vaccine that's being tested in Maryland is based on a chimpanzee virus. That may lead to some differences between the way the two work. For instance, the Canadian vaccine has been shown to offer some protection to animals that have already been exposed to Ebola. "About 50 percent of the non-human primates survived when they were given a dose of the vaccine after being given a lethal challenge of Ebola virus," Halperin says. If the Canadian vaccine is approved, it’s possible that it might one day be used as a post-exposure treatment. The Maryland vaccine, on the other hand, shows a lot of promise, Halperin says, because the type of virus it uses tends to provoke immune responses "quite easily" in humans.
It’s too early to tell if either of the vaccines will ever make it to market, given that neither has been used on humans with Ebola. But according to Lyke and Halpering, healthy individuals have been more than willing to try it out. "There’s a been huge response," Lyke says, "People just want to participate."
Halperin says that he received 150 calls over the weekend from people who wanted to participate in the trial, which was announced last Friday. "When we announced that we were doing the study, we got about 30 phone calls within 20 minutes," he says. "It’s been remarkably easy to recruit volunteers." Halperin’s trial will only involve 40 participants, so many keeners will have to be turned away once they’ve been screened. Still, it’s nice to see that degree of enthusiasm, Halperin says. Both research groups expect to have an idea of how safe their vaccines are, and which doses are optimal, after the new year.
Back to basics
There’s still an incredible amount of uncertainty surrounding the various Ebola drugs treatments and vaccines in development right now. The scientific principles behind them are sound, Lyke says, but "there’s nothing like Ebola. It’s unique in terms of viruses." That makes it harder to treat; strategies that worked for other viruses could easily fail when confronted with this particular pathogen. As a result, Halperin and Lyke are both adamant that the best interventions remain those that we already know about.
"Prior to this outbreak, Médecins Sans Frontières have always been able to contain [Ebola] using their tracking methods," Lyke says. So although "this particular outbreak has been unusual," we already know how to stop Ebola. "First and foremost, it’s about having good sterile supplies along with IV fluids and the regular supplies that medical professionals need," Lyke says. Screening people for Ebola is also crucial. Down the line, she says, a vaccine might prove useful to stop the spread of Ebola, but it’s important to keep focusing on providing healthcare workers with basic medical supplies and training.
"Ebola is a virus like many others."
And then there’s the matter of public perception. There was a lot of panic following the news of an Ebola patient in Dallas and later an Ebola patient in New York City, Halperin says, but "Ebola isn’t something that people in North America should be worrying about for themselves." In many ways, imagining a large Ebola threat in North America is hindering efforts to help people who are truly at risk. "People here should be thinking about how to support what’s going on in Africa, because this is a problem there, and our responsibility here is to do everything we can to assist."
Scholtalbers held similar opinions. "I think it is important citizens worldwide are able to distinguish fact from fable," he says. "There is an epidemic of irrational fear, while in the end, Ebola is a virus like many others."