May 21, 2018 8:27 PM

An Ebola Vaccine Gets Its First Real-World Test

Scientists have known about Ebola since 1976, and the Democratic Republic of Congo has had nine outbreaks since then. But now one shot might beat it.

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The Ebola virus kills half the people who get it, and it’s a tragically familiar disease in the Democratic Republic of Congo. Since scientists first characterized the disease in 1976, Congo has had nine outbreaks. Now it’s happening again: To date the country has seen 46 possible or confirmed cases, and 26 people are dead.

But this time is different. Four cases are in a city—Mbandaka, with more than a million people and easy transport to the megacity of Kinshasa. That has chilling implications for the potential spread of the infection. “In a rural area you might have had 10 contacts, but in a urban area after two days of fever you might have been in contact with 50, 60,” says Micaela Serafini, medical director of MSF Switzerland. “It magnifies the response.”

But this outbreak is different for another reason, too: This time there is a vaccine.

Beginning Monday, health care workers and other people on the front lines of the outbreak will receive a recombinant Ebola vaccine called rVSV-ZEBOV. After that, people who’ve been in contact with those infected with Ebola, and the contacts of those contacts, will get shots, too. It’s a strategy called ring vaccination, tailored to put the brakes on in-progress outbreaks.

While the vaccine itself is still technically experimental, it’s also the first time one has ever been deployed to fight a disease like Ebola during an outbreak. So while health officials hope it’ll fight the disease, they’re also hoping to learn how well it works under real-world conditions. “It’s under an investigational protocol that needs to follow good clinical practices, needs informed consent from all people who are going to be vaccinated, and specific people trained in deploying the research protocol,” Serafini says. “That’s quite a challenge when the clock is ticking.”

Disease hunters learn from tragedy. The Ebola outbreak whose first case appeared in Guinea in late 2013 spread throughout West Africa and killed more than 11,000 people, but it also taught scientists and health care workers important lessons about how to care for the sick. They learned better approaches to treatment and isolation centers, and they learned the importance of speedy testing and effective distribution of supplies like protective equipment.

They also learned more about the disease itself. During the Cold War, the military worried that the Soviet Union might turn Ebola into a bioweapon, and researchers at the US Army Medical Research Institute of Infectious Diseases tried to develop vaccines against it as early as the 1980s. By the time the West Africa outbreak began, researchers were working on nearly a dozen different approaches to an Ebola vaccine.

One stood out: a vaccine made by re-engineering a virus that causes a disease called vesicular stomatitis. Researchers at Usamriid and the Canadian Public Health Agency reached inside VSV and pulled out the gene that encodes a twist of sugar and protein on its surface, a glycoprotein, and replaced it with a glycoprotein from Ebola—specifically an especially nasty strain of Ebola first found in Zaire. It’s all right there in the name. Recombinant vesicular stomatitis virus is the vector, fighting Ebolavirus from Zaire: rVSV-ZEBOV. It worked really well—in rodents and monkeys. “The VSV vaccine clearly, without question, showed the most promise,” says Tom Geisbert, a virologist at the University of Texas Medical Branch in Galveston who developed the vaccine at Usamriid. Also in its favor: “It works as a single injection vaccination, where many of the other vaccines require multiple injections,” Geisbert says.

West Africa was a transcontinental catastrophe, but it was also an opportunity. Researchers from the World Health Organization and elsewhere were able to mount a trial of rVSV-ZEBOV using ring vaccination, inoculating people who’d come into contact with people with Ebola, and contacts of those contacts. Testing vaccines during an outbreak is tricky business. If you have a potentially life-saving drug, you can’t really deny it to a control group to see if they get the disease. So the team simply delayed administration to one population. In the end, more than 4,000 people got the shot, and none of them got Ebola. (Though it’s also true that the outbreak was winding down by the time of the study, meaning their exposure may not have been as high as it would have been at its peak.)

So now the pharmaceutical company Merck is donating 7,500 doses of the vaccine to Congo, and the international aid group Gavi, the Vaccine Alliance, is contributing $1 million to get it administered, according to a WHO press release.

That’s good news, but it’ll only work if WHO, MSF, and Congo’s health care teams identify the right people to vaccinate. They have to define contacts, find them, explain the vaccine and get consent to administer it, and follow up to see if it works. So here’s a cool part: Health workers from Guinea are going to provide support, training, and disease detective work. “This is West Africa lending back that expertise,” says Nahid Bhadelia, medical director of the Special Pathogens Unit at Boston University’s National Emerging Infectious Diseases Laboratories. “This is a south-south collaboration. The health care workers that went through this and gained intellectual capital are able to share it.”

Though the rules are a little different this time. In some ways, a city outbreak is easier to manage; when Ebola broke out in rural Congo last year, health care workers had to travel long distances, making sure to keep the vaccine between 60 and 80 degrees below zero centigrade. Maintaining the “cold chain” is a persistent challenge for some drugs—a home freezer hovers around zero degrees centigrade, and maintaining this level of chill requires consistent power. WHO is shipping the product in “special vaccine carriers,” the organization says, and setting up freezers in Mbandaka and Bikoro, where most of the cases are. Serafini says, the vaccine will stay fresh for a few days at up to 8 degrees, so the health care workers have a little latitude.

In rural areas, the disease doesn’t spread as far. In a city, “the population is more mobile and higher density, People are closer together and more likely to have contact,” Bhadelia says. “It’s not a slam dunk until we can get ahold of everybody they’re considering a contact.”

Still, a vaccine, even an experimental one, makes this Ebola outbreak unlike any other. “We have this new tool that we’ve never used before, and potentially that’s going to alter the dynamics,” Bhadelia says. “Now it’s about how you work in the field finding patients—the nitty-gritty of storing, administering, and monitoring a vaccination campaign.” It’s a new game. Now the players have to learn the rules.