n Ebola outbreak has once again commanded global attention, eliciting feelings of dread, anxiety, and concern.
But for a small community of researchers who have toiled for years to develop a vaccine against Ebola — one that is being used for the first time to try to contain an outbreak — it is also thrilling.
These scientists take no joy in knowing as they do the devastation that the virus can wreak. But after years of frustration with the global response to Ebola outbreaks — and a sense of helplessness in the face of so much misery — they see what’s happening now in the Democratic Republic of the Congo as a possible watershed moment, one that could forever shape the way in which health officials respond to Ebola epidemics.
“I’m of course excited that we are there. And of course it has taken too long,” said Dr. Heinz Feldmann, the designer of the vaccine that is manufactured by Merck. Targeted use of the vaccine began Monday.
For Feldmann, who spearheaded the work to develop the vaccine while he was the head of special pathogens at Canada’s National Microbiology Laboratory, the project has been the source of elation, then vexation. For years, study after study showed the vaccine worked exceptionally well in non-human primates. But the drug industry didn’t come calling — until the West African outbreak.
Now that the vaccine is being used in a real-world setting, it could prove to be a critical tool to contain outbreaks, Feldmann said, even as he stressed the importance of other ways of responding to epidemics, including isolating cases early, monitoring the health of those who have been in close contact with the infected, and ensuring safe burial procedures.
“I think it’s important that we have something to offer now and something that hopefully helps to contain this terrible disease,” said Feldmann, who now heads the National Institute of Allergy and Infectious Diseases’ virology laboratory in Hamilton, Mont.
It has not been easy to get to this point.
For years, the conventional wisdom was that vaccines or drugs to counter Ebola were not even within reach, scientifically. Ebola scientist Lisa Hensley said that was certainly the case in 1998 when she started working on the virus. But she took that as a siren call.
“I love challenges. So the minute somebody said this is something that can’t be done, it sounded like a great area for me to work in,” said Hensley, who helped in the development of animal models for Ebola and who is now associate director of science at the National Institute of Allergy and Infectious Diseases’ Integrated Research Facility.
In 2000, scientists Nancy Sullivan and Gary Nabel — now chief scientific officer at Sanofi — published the first study showing that an Ebola vaccine could provide some protection, work they conducted at the NIAID’s Vaccine Research Center. By 2005 or so, a number of experimental vaccines had been shown to work, and work well, in monkeys.
But while the NIAID vaccines were able to line up commercial partners, Feldmann’s VSV vaccine, as it is called, went unclaimed. And there was another problem: how to determine whether any of the experimental vaccines would protect people — a problem that continues to plague this field.
Regular vaccines can be tested in a few different ways. In one approach, researchers can vaccinate people and then expose them to the pathogen that the vaccine targets. That was never an option for a virus as deadly as Ebola.
Another approach is the standard randomized clinical trial. Enroll a large number of volunteers who may encounter the pathogen in their day-to-day life, and randomly assign some to be vaccinated. If researchers see more illness in the people who didn’t get the vaccine, it is considered to offer protection.
But a standard randomized clinical trial doesn’t work when a pathogen circulates as rarely as Ebola does. In the 42 years since the first known Ebola outbreak, only about 31,000 people are known to have been infected — and most of those infections occurred in the West African outbreak of 2013-2016. Outbreaks have ranged over a terrain that spans thousands of miles from West Africa to Central Africa.
Researchers could vaccinate thousands of people and follow them for years without seeing any disease in either the vaccine recipients or the control group.
Even testing during an outbreak was traditionally thought to be impossible. But the West African outbreak changed that thinking.
The vaccine now being fielded in the DRC — the VSV vaccine — was shown to be effective in Guinea in a so-called ring vaccination trial, in which people exposed to a case were vaccinated in an attempt to build a wall of immunity that cuts off the virus’s ability to spread.
In the latest outbreak, if the vaccine works as well as earlier studies suggest, it could present a paradigm shift in the way the world thinks about Ebola outbreaks.
The scientists who have long been involved in the effort are mindful of how much work it has taken to get to this point.
Tom Geisbert, a friend of Feldmann’s and frequent scientific collaborator, recalls testing the vaccine in primates in the early-2000s. His wife, Joan, who is also a scientist, also was involved in testing.
“You put your staff at risk. You put yourself at risk,” he said of the work. “And when you get something that works, do you know how exciting that is? How awesome that is not to see animals get sick?”
Added Hensley: “To me there’s no greater accomplishment than feeling that your research has had an impact on somebody’s life. That it has improved somebody’s life. Or that it has saved somebody’s life.”
Hensley, who also contributed to the preclinical testing of the VSV vaccine, acknowledged her excitement comes with a side of nerves. “There is this moment of: It’s now going into the field. And: Will it work?” Hensley said. “So in some ways you’re holding your breath.”
Like Hensley, Sullivan, who is now chief of the biodefense research section of the Vaccine Research Center, recalls the days when it was conventional wisdom that there could not be an Ebola vaccine.
“The belief was that the virus was so aggressive that you can’t find a vaccine that would protect,” she recalled.
Now, Sullivan is excited to see the Ebola vaccine being used. But she admitted to feeling torn about seeing it being deployed in an outbreak at all.
“It’s tainted with the knowledge that people are sick and dying. I think that tempers the excitement,” she said. “Because there’s a reality that accompanies that that’s very, very sad.”