Fever was the first symptom to grip the crab-eating macaques in their high-containment laboratory on an island off Texas after being infected with the newly discovered Bundibugyo strain of
ebola. Then came the weight loss, the rectal bleeding and nosebleeds, while scientists in space suits drew blood to see how the monkeys’ immune systems struggled to fight the aggressive virus.
But the three monkeys that had received a newly developed vaccine to protect against the understudied strain showed no symptoms of the disease, which eventually killed two-thirds of their unvaccinated companions.
It was 2011, and virologist Thomas Geisbert’s work developing the vaccine was done. If the vaccine had protected primates from the
Bundibugyo strain of ebola, it was highly likely to protect humans. Yet with an outbreak now raging in the Democratic Republic of Congo and Uganda, Geisbert’s promising vaccine hasn’t been deployed at all—or even put through human trials—because there hasn’t been the funding or interest.
And it could take months to test its safety and efficacy, even as the Bundibugyo virus causes widespread suffering. “We’ve got the rVSV Bundibugyo vaccine sitting on the shelf,” says Geisbert, an immunology professor at the University of Texas Medical Branch in Galveston. Recombinant vesicular stomatitis virus “rVSV” vaccines use a harmless version of that virus to deliver the genetic instructions needed for the body to fight the disease.
Hundreds of people
have been infected in the current outbreak in Central and East Africa, and around 200 have died. Public health officials have been scrambling to develop a vaccine, with the World Health Organization identifying Geisbert’s as the most promising candidate.
Geisbert’s work began in the early 2000s as a defense project focused on other strains of ebola. In the wake of September 11 and concerns that terrorists may deploy ebola and similar pathogens as biological weapons (something the Soviet Union had investigated during the cold war), the US Army provided funding to develop a vaccine for the virus.
His first big breakthrough in 2003 found monkeys could be protected from ebola with a single injection of the vaccine he had developed. But when Geisbert first published his findings a few years later, he found little commercial interest.
“There just wasn’t a global market for an ebola vaccine,” he says. “It’s not a moneymaker, nobody really wanted to pick it up.”
That in part led Geisbert to look at whether this vaccine could protect monkeys from different strains of the disease, which would make it cheaper and easier to develop and mass produce. He
tested a blend of vaccines against three of the four ebola viruses known to harm humans with success and published the results in 2009.
Interest in taking them beyond the lab reached a critical mass during the
2013 to 2016 ebola epidemic, when the Zaire strain—the most common—infected 28,600 people and killed 11,300 in West Africa. The virus’s rapid spread and high mortality rate prompted a race to develop a vaccine. That included one developed by pharmaceutical giant Merck in part thanks to Geisbert’s work. Dubbed Ervebo, it was deployed in a “ring” where contacts of the infected are vaccinated, effectively creating a buffer zone that limited the spread of the virus.
The vaccine’s success earned Geisbert a spot among Time magazine’s “ebola fighters,” whom the publication dubbed its people of the year in 2014.
But Geisbert’s initial study omitted one strain of ebola, Bundibugyo, because it has lower fatality rates and has caused just three outbreaks. That includes a 2012 outbreak that killed 30 people over about three months in the DRC but was contained fairly quickly due to contact tracing and isolation.
“We thought that’s probably the one that’s least likely to pop up,” Geisbert says. “We guessed wrong.”
Concerned by that knowledge gap, in 2011 he decided to modify a vaccine, which led to the crab-eating macaque study. In the same study, he also finally tested a blend of existing ebola vaccines on the Bundibugyo strain, but they didn’t provide 100-percent protection.
If the 2012 outbreak had occurred after the major Zaire outbreak, Geisbert says, it’s possible pharmaceutical companies might’ve been more keen to commercialize a vaccine that protects against the Bundibugyo strain.
But with the present outbreak rivaling the 2013 to 2016 one in terms of scale and scope, efforts to play catch-up are going into high gear. Geisbert suspects WHO’s experience with Ervebo is one of the reasons they favor his vaccine candidate, which is basically “Bundibugyo Ervebo,” he says.
WHO also noted the success of a similar rVSV-based vaccine targeting the Sudan strain of ebola in a ring vaccination trial in 2025.
The rVSV-based Bundibugyo candidate’s suitability for ring vaccination was backed by a 2023 study showing most of the monkeys were protected from the virus even after they were exposed if they had been vaccinated. That is crucial for ring vaccination to work. While the researchers vaccinated the monkeys an unrealistically quick 20 minutes after exposure, the proof of concept sets it apart from Moderna and the University of Oxford’s candidates under development.
“There hasn’t really been much development since that 2023 study, because we weren’t really expecting to see that strain and also because historically it's been associated with lower-rate mortality as well,” said Courtney Woolsey, the lead author on the paper (Geisbert was a coauthor) and an assistant professor within the University of Texas Medical Branch.
“Nobody really makes money off these vaccines,” she adds, “so there are funding barriers as well to advance these vaccines where people likely aren’t going to make money.”
The nonprofit Coalition for Epidemic Preparedness Innovations has offered funding of up to $3.2 million to prepare and start testing the material needed to manufacture Gesbert’s vaccine, which would be the first step towards human trials.
The “extensive safety data and prior regulatory experience” from the rVSV-based vaccines used to combat the Zaire strain “could help expedite approval pathways if it is shown to be successful,” Rachael Bonawitz, filovirus disease programme lead at CEPI, tells WIRED over email, adding that developers would also be able to build on existing manufacturing processes.
“Even if it’s not used in this outbreak, hopefully there will be clinical material that can be used in humans available for the next outbreak,” Geisbert says, “because it will probably pop up again.”
Even as it shows promise, there is still a chance his vaccine won’t work. Scientists have not been able to obtain a live Bundibugyo virus sample for testing due to stretched resources in the DRC and the logistical and bureaucratic complexity of obtaining and transporting refrigerated blood back to the US. While scientists believe the current strain is around 98-percent similar to the strain that caused the previous outbreaks, that unknown 2 percent presents a risk the vaccine won’t be as effective as it was against the previous strain.
“When you look at the sequences it’s not different enough that I would predict that there would be a problem, but nothing’s foolproof,” Geisbert says.
The International AIDS Vaccine Initiative in New York will prepare the vaccine candidate for production. The nonprofit biomedical research organization focuses on developing vaccines for global diseases where there is little financial incentive for development.
“The baton has been handed off, and I just sit back and hope that it works, whether it’s the vaccine, whether it’s somebody else’s vaccine,” Geisbert says.
<small>Source: Wired</small>
