What will it take to get a vaccine for the Ebola strain driving the current outbreak?

"We decided, because of the urgency, that we would go ahead and accelerate vaccine development," she says.

Even with all this cash, it'll be months before researchers can figure out whether the vaccines in development can offer meaningful protection against this deadly disease — and even longer before they're widely used. But given that the DRC outbreak is already one of the largest on record and shows no sign of slowing down, any future vaccine could still make a difference.

"We are very happy to see commitment to fast-track candidate vaccines," Anaïs Legand, a WHO technical officer said during a Wednesday press conference. "They will still need to undergo testing," including clinical trials that comply with ethical guidelines.

Discussions on how to conduct those trials are ongoing, according to briefings by World Health Organization officials. Historically, the U.S. has had a major role in researching experimental vaccines and treatments amid ongoing outbreaks. Now that the Trump administration has withdrawn from WHO and dismantled much of the U.S. infrastructure that supported this research, it is unclear what role the U.S. will play.

For instance, during the 2014 Ebola outbreak in West Africa, the Division of Clinical Research at the U.S. National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, partnered with affected countries to design and run clinical trials of the vaccine that eventually got approval in 2019.

"That division is now gone," says Elizabeth Higgs, who was the associate director for strategic research partnerships within the Division of Clinical Research at NIAID. She left NIH in February and is now working with WHO on planning for therapeutic and vaccine trials amid the ongoing outbreak.

"If this outbreak would've been two years ago, then we would have already mounted an emergency research response from the NIAID/NIH," she says. "But I think we're doing very well without the NIH working with the global community," she says, referring to disease preparedness research networks set up by the WHO.

Vaccines in the works

Three vaccine makers — IAVI, a non-profit that develops vaccines, University of Oxford and biopharmaceutical company Moderna — are receiving the funds from CEPI. Each vaccine candidate has strengths and weaknesses in terms of how quickly it might get developed and approved.

IAVI will receive up to $3.2 million to develop its candidate, which is the furthest along in terms of testing. It uses the same approach as an approved Ebola vaccine, called Ervebo. IAVI's vaccine uses a harmless virus, called a vesicular stomatitis virus or VSV, to deliver instructions to the immune system on how to recognize the Bundibugyo species of Ebolavirus.

Thomas Geisbert, a vaccine researcher at the University of Texas Medical Branch, helped develop this vaccine over 15 years ago, after the first Bundibugyo outbreak in 2007. In a 2014 study, he and his colleagues showed their Bundibugyo vaccine worked in monkeys.

"We vaccinated monkeys one time, which is good for outbreaks because you need something that works quickly, and then we exposed those monkeys to Bundibugyo and they were all protected, they didn't even get sick."

A subsequent study, published in 2023, showed vaccinating monkeys 20 to 30 minutes after exposure also offered high levels of protection. That's key, says Geisbert, since vaccinating soon after a possible exposure — a strategy known as ring vaccination — has been critical to stamping out prior outbreaks.

But there currently are not enough doses of IAVI's vaccine to conduct larger clinical trials. Making more could take seven to nine months, according to the non-profit, given it takes time to grow the vaccine viruses.

The two other candidates could be ready faster but haven't yet been studied in animals.

One is from the University of Oxford, which will receive up to $8.6 million from CEPI. That vaccine uses the same strategy as the Oxford/AstraZeneca COVID-19 vaccines, but targets the Bundibugyo species of Ebola. Oxford researchers have partnered with the Serum Institute of India, a major vaccine manufacturer, and say that doses could be ready within one or two months.

Finally, CEPI is awarding Moderna up to $50 million to develop an mRNA vaccine against Bundibugyo. In 2018, researchers showed that an mRNA vaccine provided 100% protection against the Zaire species of Ebola in guinea pigs. Those animals needed two doses for protection, as opposed to one.

"That's not ideal when you're trying to control an outbreak," says Darryl Falzarano, a vaccine researcher at the University of Saskatchewan. "You need rapid time to protection."

It's unclear whether Moderna is pursuing a one- or two-dose strategy. The company did not respond to a request for information.

The challenge of clinical trials

Months from now, all of these candidates will need to be tested in clinical trials in the Democratic Republic of Congo or Uganda, where the Bundibugyo species is currently spreading.

Conducting clinical trials in any outbreak can be hard, since it's tough to know where cases will be in the future. This particular outbreak could be especially difficult, given the ongoing conflict in northeast DRC.

"It's a very challenging area to work in," says Laurie, of CEPI. "And unfortunately there is just so much mis- and disinformation about vaccines, a lot of distrust in the communities." Rumors circulating on social media claim Ebola isn't real, or that aid workers are killing patients who enter clinics. Already, community members have attacked several clinics.

That environment could make it difficult to enroll participants in a clinical trial and track whether a candidate vaccine protects them from Ebola, says Laurie. "We all need to start beginning now to think about how we engage communities and community organizations in helping get ready even to test these vaccines."

Higgs, the former NIH staffer now advising WHO on these trials, says that's happening now. "We're doing everything we can to establish trials that are going to quickly and rigorously assess the safety and efficacy of these candidate products."