Last week, Uganda announced uplifting news about the Ebola outbreak that surfaced there in mid-September: The last known patient had recovered and been discharged from a hospital. Health officials hope that signals the spread of the virus has slowed dramatically, if not stopped altogether. Yet the aggressive containment efforts that led to the waning of the outbreak also means a quickly arranged trial of experimental ebolavirus vaccines faces formidable hurdles. The goal of the so-called ring trial is to test the efficacy of the vaccines by giving them to contacts of known cases. But the number of potential participants is dwindling fast.
The plan is still to start the trial as soon as this week, but it may have to be called off or redesigned. The issue is sensitive, given the amount of effort put into securing vaccines, obtaining permits, and raising roughly $9 million in funding for the trial. Multiple people close to the study—including three Ugandan researchers—refused to speak to Science on the record about its prospects. But Mark Feinberg, who heads IAVI, a New York City–based nonprofit that has the rights to a Sudan ebolavirus vaccine, says, “Whether the study will start or not I think is an open question.”
According to the World Health Organization (WHO), as of 25 November, Uganda had 141 confirmed cases, 55 of whom had died. WHO tallies include another 22 deaths as likely due to the virus, which had spread, alarmingly, to Kampala, the heavily populated capital.
The last confirmed case was diagnosed on 13 November, save for a stillborn baby on 27 November whose mother had already recovered. After 42 days have passed without a case, the outbreak officially will have ended. But epidemiologist Mike Ryan, director of WHO’s Health Emergencies Programme, cautioned at a press conference last week that there were still “significant gaps in tracing some of the chains of transmission,” which means new cases and their contacts may soon surface. “Ebola always has a sting in its tail,” he said.
Researchers had hoped for a chance to test new Ebola vaccines. A vaccine has been approved since 2019 for the Zaire ebolavirus, which has caused multiple outbreaks in several countries, including a widespread epidemic in West Africa that ran from 2013 to 2016. But monkey studies suggest that vaccine will not work against the genetically distinct Sudan ebolavirus behind this Uganda outbreak.
When the new Ebola cases surfaced, several vaccines for the Sudan ebolavirus were in development, and Ugandan health officials on 2 December approved testing three candidates. But at the start of the outbreak no manufacturer had enough doses in vials to ship. Doses of vaccines developed by the nonprofit Sabin Vaccine Institute and, separately the University of Oxford may arrive in Uganda over the next few days. An expert committee organized by WHO says the most promising of the vaccines, developed by Merck and licensed to IAVI, has lagged farther behind because Merck did not realize until nearly a month into the current outbreak that it had 100,000 old but viable doses frozen in bulk supplies.
The vaccines may arrive too late to assess their worth, however. To be eligible for the ring trial, participants must have been exposed to an infected person within 21 days. As of this week, only a few hundred people—about 20 per case—remain eligible. Without new cases, that number decreases each day.
Ana Maria Henao-Restrepo, WHO’s main representative helping organize the study, said at last week’s press conference the trial was “imminent” but had no set launch date.
Even if the ring trial doesn’t launch, Feinberg says he hopes Uganda will stage a phase 1 safety study of the IAVI/Merck vaccine—most likely in health care workers. If it triggers immune responses that mirror the ones seen with the successful Zaire ebolavirus vaccine, the new data, combined with studies that show immunized monkeys have solid protection against the virus, could persuade regulators to approve it for use in future outbreaks.
The Uganda outbreak highlights the need for a more streamlined outbreak response system. “People got these doses together really, really quickly,” says Nicole Lurie, U.S. director for the Coalition for Epidemic Preparedness Innovations—but perhaps not fast enough to save lives. “We need a reserve of [investigational] vaccines so they’ll be at the ready for the next outbreak,” she says.
One answer, says Seth Berkley, CEO of Gavi, the Vaccine Alliance, is to stockpile experimental vaccines on the continent—for Ebola and other emerging diseases—and agree on trial protocols ahead of time. “We have to crack this,” he says, noting that to store COVID-19 vaccines GAVI supplied Uganda and many lower income countries with –80°C freezers that could be repurposed for other vaccine stockpiles.
Berkley acknowledges that creating and maintaining stockpiles would cost money, and it also means periodically throwing away vaccines that expire and replacing them. Still, he says, “It would have been awfully nice to have had 100,000 doses ready to go at the start of this outbreak. That’s where I think we have to go next.”