A clinical trial of vaccines targeting the Ebola Sudan virus is starting this week in Uganda, with first doses going into arms potentially on Tuesday. Already, though, this effort has taught the World Health Organization and partners two important lessons.
They’ve learned they can get clinical trials to test countermeasures for rare but dangerous pathogens up and running far more quickly than eight years ago, when a similar effort was launched to test vaccines as Ebola Zaire raced through three West African countries. That effort took more than five months. This one has taken roughly 80 days.
But they’ve also learned that the work needs to be done faster still — and that there are ways to streamline these critical endeavors. They will, though, cost money.
The current outbreak encompasses 164 confirmed and probable cases and 78 confirmed and probable deaths. But there hasn’t been a new Ebola case in Uganda in more than two weeks, and it’s looking very much like the outbreak has been brought under control. Unless cases have been missed and transmission flares up again — an event no one hopes for — this clinical trial will not be able to determine whether any of the three vaccines being tested actually works; it could, however, be useful in evaluating their safety.
Had these experimental vaccines been available to push into the field earlier, in ready-to-use vials, that outcome could well have been different. But Ebola Sudan outbreaks are rare; in fact this is the first in a decade. Having vaccine doses in vials at the ready could well mean making vaccine that would end up being discarded, doses that would need to be replaced. And not just for Ebola Sudan, but for a number of other rare but high-consequence pathogens like Marburg virus or Nipah virus, said Mike Ryan, who heads the WHO’s health emergencies program.
“If we’re being truly strategic, what we should be doing is have ready-to-go trial platforms in a set of countries with products ready to go. But that requires … a huge effort on everyone’s part and potentially an effort that doesn’t result in immediate results,” Ryan said in an interview with STAT. “You could develop these products, have them in clinical lots, you could develop the trials platforms, and never use them.”
This is beyond the means of the current developers of the Ebola Sudan vaccines — two nonprofits and a university-based institute, all of whom are also trying to advance other needed vaccines for rare diseases.
Ryan suggested the world needs to think about this type of investment as a form of defense spending, pointing to the example of the damage the Covid-19 pandemic did to humankind and to the global economy to explain why health security investments make sense.
“If I gave you that scenario three years ago and said it’s definitely going to happen, and I need $100 billion to stop it from happening, that would be good value,” he said. “It’s a rounding error in the global defense [spending]. The big question is, what is defense in a citizen’s view of the world?”
Seth Berkley, CEO of Gavi, the vaccine alliance, agreed, telling STAT in a separate interview that he thinks it’s time the world invests more in being ready to battle dangerous disease outbreaks more quickly. He noted the U.S. maintains a large stockpile of smallpox vaccine because it views the eradicated disease as a bioterror threat. When that vaccine reaches its expiration date, it is destroyed and replaced.
“I think it’s a little bit of a disgrace that we didn’t have Ebola Sudan vaccines in a vial ready to test,” Berkley said on Monday. “Because had we had that, three days into the new outbreak we could have [started vaccinating] and showed that the vaccines worked or didn’t work.”
The three vaccines are being developed by the Sabin Vaccine Institute, Oxford University’s Jenner Institute, and the International AIDS Vaccine Institute or IAVI, as it is better known. Doses of the Sabin vaccine are already in Uganda, and the Oxford vaccine is on its way. The IAVI vaccine, which was made by Merck, is expected to arrive next week.
When the WHO, Uganda, and other partners decided to try to conduct the clinical trial back in late September, there were sufficient supplies of the Sabin and the IAVI vaccine. But they were frozen and in bulk, a way vaccines can be safely stored for long periods of time without losing potency. The Oxford group had to place an order with the Serum Institute of India to produce doses of its vaccine.
Ana Maria Henao-Restrepo, who heads WHO’s R&D Blueprint effort to develop drugs, diagnostics, and vaccines to respond to outbreaks of rare and dangerous pathogens, said the Oxford-Serum Institute partnership managed to produce 90,000 doses in 60 days — a stunning feat. The other two vaccines had to go through what’s called fill and finish, where bulk vaccine is transferred to vials that can be used in the field.
Henao-Restrepo, who took part in the interview with Ryan, said prior to this, people would have suggested that having vaccine in bulk was adequate preparation for starting a trial of untested countermeasures against an outbreak illness.
“Well, no, it takes 60 to 90 days to move the vaccine doses from bulk to vials, so having them in bulk is not enough,” she said.
Berkeley said that during the West African Ebola outbreak — the largest the world has ever seen, with more than 28,000 cases and more than 11,000 deaths — the world was ready to pay whatever was needed to control the dreadful epidemic.
“‘Seth, money’s no object. Whatever it takes,’” he recalled being told. “And a few months later, when I went to raise money for the Ebola [vaccine] stockpile, people were like: ‘Ebola? That’s yesterday’s problem.’”
“After having that West African outbreak, you would have thought we would have Ebola Sudan and Ebola Bundibugyo” — another rare Ebola species — “in vials ready to go with approved [clinical trial] protocols. And we didn’t,” he said.
While the job of getting doses to test was underway, the WHO, the government of Uganda, and other partners were working through the myriad issues that need to be agreed to before a clinical trial can start. Henao-Restrepo believes that what has been achieved here will lay the groundwork for future responses.
“The next time we have … a Sudan ebolavirus outbreak, we will have the protocol. Everything ready. People will know how to do it. We know now how to train the locals very quickly. All this is different,” she said.
Ryan agreed, but stressed that more investment ahead of time would make the world a safer place by lowering the risk that Ebola or other dangerous pathogens pose, both in the countries where they occasionally emerge and in others further afield that sometimes have to respond to imported infections. Seven countries, including the United States, had imported Ebola cases during the West African outbreak.
“What we’re saying is that we’ve demonstrated that we can do it much faster, much quicker, with the country at the center, with ethics, with all of those issues being properly dealt with. We can go fast without cutting any corners. And we can do that even faster if we invest in the sort of the countermeasures platforms that we need for the pathogens that we’ve identified as being important,” he said.
“It can’t just be done piecemeal every time there’s a crisis,” Ryan said. “Every time there’s an outbreak we do it again — we roll the rocks up the hill. We need to do that much more strategically.”