Behind the Life-saving Ebola Vaccine is a Story of Missed Opportunity
Nurses working with the World Health Organization prepare to administer vaccines at the town all of Mbandaka during the launch of the Ebola vaccination campaign. (Photo by Junior D. Kannah/AFP)
In April 2005, Canadian microbiologist Steven Jones walked into an isolation ward clad in protective gear, picked up a chubby, burbling baby boy and fed him a bottle. Jones had arrived in Angola the month before, part of an international relief effort to help quell an outbreak of the deadly Marburg virus. Two days later, that baby boy was dead, and Jones — who had recently helped develop a vaccine he believed could have saved him and hundreds of others — was plagued by the question: what if?
“We had something that could stop the disease in its tracks,” said Jones in a recent interview with FRONTLINE. “But we weren’t able to use it.”
Jones’ research team had discovered a vaccine, dubbed rVSV-ZEBOV, that was 100 percent effective in priming the immune systems of mice and monkeys to fight off Ebola and Marburg. The vaccine hadn’t been tested in humans, but that didn’t stop Jones’ team from bringing vials to Angola. “If we had had an accident, we would have taken it, no question,” Jones said. “But it was awful knowing that we had something that could potentially stop that outbreak, and we couldn’t.”
Angola’s Marburg outbreak killed 300 people. In the years since, thousands have died of Ebola, another hemorrhagic fever virus. But underfunding and a lack of interest from pharmaceutical companies meant that rVSV-ZEBOV, which was known to work as early as 2003, took more than a decade to make it to the front lines of Ebola response.
In late 2014, at the height of the West Africa Ebola epidemic that eventually killed more than 11,000, pharmaceutical company Merck finally inked an agreement and started the vaccine’s clinical trials. The experimental treatment remains unlicensed, but it is currently protecting hundreds of thousands across the Democratic Republic of Congo, where the world’s second-largest Ebola outbreak has killed more than 1,800 people and rages on.
Developing new reliable treatments for disease often requires the perfect confluence of time, money and scientific breakthrough. That western governments and private corporations missed an early chance to cure what they saw as a niche African disease was no surprise to Jones.
“It’s called the ‘valley of death,’ between those very first experiments and the first clinical trial,” he said. “That’s where good ideas go to die.”
In 2015, after Jones started a stint in the private sector, he was asked to go to Sierra Leone alongside consulting group McKinsey to help support the country’s response to the outbreak in West Africa. The country was essentially shut down. For Jones, it was like going back in time. “Eleven years later, we’re there, and thousands of people have died, because we weren’t fast enough,” Jones said. “And the vaccine still wasn’t ready.”
Prelude To An Epidemic
In the late 1990s, Ebola research was a sleepy field. Since the virus was first identified in 1976 it was considered a scientific enigma, but not a high priority. Jones jumped into Ebola and Marburg research at Canada’s high-security National Microbiology Laboratory because he was fascinated by immunology and designing animal experiments. At the time, his group’s biggest incentive for producing an effective vaccine for the viruses was the risk of an errant needle. “We wanted something that would protect us from death if we injected ourselves in the lab by accident,” he said. “We were the people routinely using Ebola and needles, and therefore, at risk of becoming infected.”
After 9/11, bioterrorism, and specifically Ebola and Marburg (which the former Soviet Union had previously tried to weaponize) quickly topped the list of potential threats. Suddenly, millions of dollars started to flow into the field.
“There wouldn’t have been a vaccine had there not been an increase in funding for bioterrorism,” said David Heymann, a Centers for Disease Control and Prevention veteran who was deployed by the agency during the first three major Ebola outbreaks. He currently chairs the WHO’s scientific and technical advisory group on infectious hazards.
Between 2001 and 2014, the U.S. spent more than $79 billion on biodefense-related programs, including bolstering its own stockpile of vaccines and drugs. “Nobody developed this vaccine for outbreaks in Africa,” Heymann said.
After Jones and his colleagues returned from Angola in 2005, haunted by deaths they couldn’t prevent, they asked the Canadian government for $6 million to conduct clinical trials of their vaccine in humans. They only received $2 million, so it was only tested in macaque monkeys. When the West Africa Ebola outbreak began, the vaccine still hadn’t been through human trials. “I was really annoyed, and convinced [the funding agency was] wrong, but I also couldn’t blame them,” Jones said. He acknowledged that there is only so much money governments can invest in experimental research, but he said it was the “wrong call.”
In 2005, desperate to encourage rVSV-ZEBOV to market, Jones and his colleagues started trying to find a pharmaceutical company that could take over testing and manufacturing the vaccine. One small article headlined “Wanted: manufacturer for Ebola and Marburg vaccine” ran in the Canadian Medical Association Journal.
In 2010, a small Iowa company called NewLink Genetics licensed rVSV-ZEBOV from the Canadian government (which had already spent at least $5.3 million developing the drug) for $205,000. “They were literally the only people interested. Merck, Wellcome, all of the big companies weren’t interested,” Jones said. “No one thought the outbreaks would be big enough. But then West Africa happened.”
In August 2014, as political pressure to respond to the crisis mounted, the U.S.’s Defense Threat Reduction Agency, part of the U.S. Department of Defense, awarded NewLink a $1 million contract. Trials of the drug started in Silver Spring, Maryland, in October 2014.
One month later, at the height of world’s most devastating Ebola outbreak — four years after NewLink first got the vaccine patent — two Canadian researchers called on their government to cancel the agreement with NewLink and finally find a reliable manufacturer for the vaccine. “Africa’s needs are too urgent for half measures,” they wrote in the British medical journal The Lancet. “The choice of a patent over patients in this instance is unpardonable.”
Within a week, NewLink had signed a licensing and collaboration deal with Merck, and soon after the smaller company’s stock more than doubled. NewLink made $50 million on the deal and is still set to receive “escalating royalties on potential commercial sales … ranging from low to high single digit, on increasing levels of annual net sales worldwide,” according to one of the company’s quarterly reports. (Last year, according to a spokesperson, Merck spent $10 billion on research and development.)
It was too late. The only reason clinical trials of rVSV-ZEBOV started in Guinea, near the end of the last major outbreak, Jones said, was because Canada eventually donated 800 vials of its own stockpile to the WHO in October 2014. (The year before, the government of Canada paid a German company $827,000 to manufacture 1,500 experimental vials of the vaccine.)
“Had NewLink (or others) conducted basic … trials earlier, the vaccine could have been deployed in West Africa during the outbreak and saved lives,” Doctors Without Borders wrote in a report. “This wasted opportunity nevertheless netted NewLink a substantial profit, despite it not having advanced the development of the vaccine.”
Lisa Miller, NewLink’s director of investor relations, declined to comment for this story, deferring all questions regarding the vaccine to Merck.
At the beginning of 2016, Merck signed an advance purchase commitment for the drug, which it renamed V920, with the vaccine-promoting organization Gavi. The deal promised Merck at least $5 million in sales once the vaccine was licensed and required Merck to produce 300,000 doses of the vaccine before the next outbreak. Those are the precious and limited doses that are currently protecting thousands in Congo right now.
Stopping The Spread
The current Ebola epidemic in the Democratic Republic of Congo is now the world’s second-largest since 1976. More than 2,600 cases have been identified, and about two-thirds of those infected have died so far.
According to Gavi’s CEO Seth Berkley, this current outbreak is exactly why his organization required a commitment to manufacture vaccines before — not during — an outbreak. “The worry was that Ebola only affects the very, very poor in some of the poorest countries in the world, and that there wasn’t really a [lucrative] market,” he said.
As heath workers scramble to stop the spread of the virus, 178,000 people across the country have been vaccinated with V920, which is administered by a shot to the arm. The drug, which many now call the “Merck vaccine,” is still unlicensed, so it is being administered as an experimental drug under supervised clinical trial. Dr. Jean-Jacques Muyembe, a Congo virologist who was the first to treat a case of Ebola in 1976, is overseeing the country’s response to the virus as well as vaccinations.
When determining who gets the vaccine, doctors employ a “ring” strategy, similar to how smallpox was eradicated. As new cases of Ebola are identified, health workers make lists of people who may have touched a victim or encountered their bodily fluids within 21 days — the longest period in which symptoms are likely to occur — as well as an outer ring: anyone else who made contact with a potentially undiagnosed infected person.
The WHO is using this approach, Berkley said, because there are not enough doses available to vaccinate everyone in the affected areas. As of early August, since the U.S. Food and Drug Administration informed the WHO that a half-dose of live vaccine was as effective as a full, Merck has guaranteed it can provide at least 400,000 additional doses. It is also working to produce more in the United States and Germany within 6 to 18 months.
However, if there’s another major outbreak in the next few months, there likely won’t be enough of the vaccine to go around. That’s one reason why medical teams in nearby Uganda are testing another two-dose vaccine manufactured by Johnson & Johnson; more than 6,000 people there, mostly Ugandans, have been vaccinated, with 800 participating in a clinical trial. (Officials in Congo, so far, have rejected calls to start testing the second vaccine, saying that it could further complicate an already chaotic situation.) Simultaneously, two promising experimental drugs made from the antibodies of Ebola survivors — mAb114 and REGN-EB3 — are being administered on an emergency basis as scientists enroll willing volunteers into clinical trials.
Despite all these potential therapies, Berkley said the situation on the ground is still “dire.” On a recent trip to Congo, he was shocked that around 30 to 40 percent of new cases aren’t being linked to other known cases. He worries that V920’s impressive efficacy is causing complacency in threatened communities, where health care workers aren’t always able to trace chains of transmission.
In Butembo, the heart of Congo’s outbreak, Berkley — who is trained as an epidemiologist — saw some of the hundreds of community health workers going house to house; about 1,000 to 1,500 new people are vaccinated every day. But vaccinating hundreds of thousands more won’t stop the outbreak. “This problem is going to be solved by making sure there’s good public health and epidemiological follow-up. And then the vaccine is going to be extremely useful,” he said. Although the vaccine has prevented this current outbreak from blowing out of control, Berkley remains worried.
Jones, who earns royalties on V920 but has since left lab research behind, said his professional arc has been one largely of disillusionment. Though he understands the complicated factors involved in developing the vaccine, the delay is something he carries every day.
“I used to think of Ebola as a biomedical, technical problem, but the reality is that this is a problem of political and economic instability and inequality,” Jones said. “If this outbreak was happening in the U.S. or Canada, we would apply the vaccine and the systems we have in place, and it would be crushed within weeks.”