Of all the vaccines developed in the West, though, the Oxford-AstraZeneca entry has been most beset by controversy. A dosing error — or a serendipitous discovery, take your pick — in clinical trials caused confusion over efficacy. Early trials also did not include enough people over 65 to prove the vaccine protects the elderly, leading several European countries to restrict use in that age group, while the United States waits for more data.
Then, South Africa suspended its Oxford-AstraZeneca rollout after preliminary findings that the vaccine provided only “minimal protection” against mild and moderate covid-19 caused by the virus variant found there. Now an emerging chorus of people, including health-care workers in France and teachers in Italy, is saying they’d rather get the Pfizer-BioNTech or Moderna shots.
The Washington Post spoke with Gilbert and Pollard in separate video calls about conducting research under intense public scrutiny, how worried the world should be about the rise of variants and what it will take to get the pandemic under control.
Should we be freaking out about variants?
Both scientists stressed that virus mutations are to be expected — especially in a novel coronavirus, which is evolving to survive in its new host, a human. The B.1.1.7 variant discovered in Britain is 30 to 70 percent more transmissible, and it is spreading fast in the United States and Europe. Early research suggests it might cause more severe illness. The variants first identified in South Africa and Brazil are also worrying, perhaps more so.
“And as we start to see immune selection pressure on the virus, it’s likely to make mutations that will evade the immune response, either from the first infections or from the vaccines,” Gilbert said.
But she offered reassurance that the virus can mutate only so much and remain a contagious pathogen. The spike protein that the virus uses to bind to a human cell will keep changing, but those reconfigurations in structure are not infinite.
“So whatever the spike protein turns into, the immune system can make antibodies against it, so there’s nothing that’s so bad,” she said.
What would it take to adapt the vaccine for variants?
Gilbert has long worked on seasonal flu vaccines, a complex guessing game but a well-established one. She said all vaccine developers may need to roll out new versions of their coronavirus booster shots every year to confront the variants.
“It happens every year for flu vaccines. And nobody really thinks about it,” Gilbert said.
The Oxford labs are working on at least 10 new versions of their vaccine to combat the “variants of concern” identified in England, Brazil and South Africa. The researchers said AstraZeneca could, if needed, have millions of doses of a new version ready for distribution in the fall.
Gilbert described the process: First they must test the new vaccines in the lab, then manufacture initial batches, then do small clinical trials to show safety, then wait for trial volunteers to generate an immune response.
“That all takes time. And then that data package has to be put together and put in front of all the regulators around the world that we are going to ask to allow this strain change. And they can’t do that overnight, either,” she said. “So, it sounds like quite slow saying we’ll have it ready for the autumn. But we are actually thinking of rollout in the autumn. The whole process.”
Just as with successive versions of seasonal flu vaccines, Gilbert said, the developers do not need to reinvent the wheel each time. She would expect regulators to accelerate the process.
“We’re not going to be doing full efficacy trials again,” she said. “There isn’t time to do efficacy trials again.”
Pollard said it is still possible that existing vaccines can break the back of the pandemic — if they are rolled out quickly. “But if that is wrong, then I think we might be in a position where we need to tweak the vaccine regularly,” he said.
What about people who want Pfizer or Moderna rather than Oxford-AstraZeneca?
The Pfizer-BioNTech and Moderna vaccines have shown about 95 percent efficacy against symptomatic covid-19 in their clinical trials. The Oxford jab was 62 percent effective or perhaps 70 percent, depending on how the data was processed.
Pollard said he understood the concerns expressed by the public.
“I mean, for me personally, I would take whichever vaccine is offered, because the most important thing with vaccination is to have the dose in your arm,” he said.
“But to be very specific about your question, which I think is a good scientific question: The problem with the trials, unless you run the trials head-to-head, you don’t really know whether a 95 percent figure on trial and 62 percent in another trial mean the same thing.”
Gilbert said she was eager to see data on the real-world effectiveness of Britain’s vaccination campaign.
“They will have that for Pfizer and AstraZeneca in the not-too-distant future,” she said. “And we’ll be able to see when you immunize all the over-80s and all the over-70s with one dose, what happens? And that’s what we really want to see.”
Will the vaccine stop both infection and transmission?
A big unknown is how well any of the existing vaccines work to stop infection and the spread of the virus. Gilbert and Pollard suggested it was possible to slow transmission but very difficult to stop it.
“In order for this virus to survive, it’s going to have to select variants which can still transmit in populations who are immune,” Pollard said. “So I think we are going to see ongoing transmission of this coronavirus. And I don’t think that’s going to end over the years ahead. We shouldn’t be surprised by that, because we live with coronaviruses normally, anyway.”
Instead, the scientists stressed the ability of vaccines to protect against serious illness.
“Most of the vaccines are giving around 100 percent protection against hospitalization and deaths,” Pollard said. “To me, that’s the index. . . . So if that is the case, then these vaccines are essentially all doing the same thing for what we really care about, which is keeping people out of hospital and dying.”
Gilbert said the current class of the Oxford vaccine and others should still offer some protection against serious illness in patients infected by the emerging variants.
“So we expect to see still pretty good protection against hospitalization and severe disease, even if we don’t change the vaccines,” she said. “I think we are likely to see a decline in vaccine efficacy. But it won’t be a complete absence of vaccine efficacy.”
What's the best way to get more doses to the world?
“From a global perspective, I think that’s really where I have my biggest fears, because we’ve got so few doses at this moment for the world,” Pollard said. “And it feels like climbing the most enormous mountain to get to a point where the supply and distribution of these many different products go to all those corners of the world where people really need access to them. So I think that’s the bit that I’m most worried about for the year ahead, is how do we get equity?”
Should governments continue to invest in new vaccine candidates? Should they focus on expanding production capacity for the top vaccines that have emerged so far? Should they force collaboration? French pharmaceutical company Sanofi is helping its competitors Pfizer and BioNTech produce their vaccine, after a strong nudge from the French government. And since Merck abandoned its two vaccine candidates last month, it is looking for ways to help.
But the Oxford researchers said that although they’re all for collaboration, it can be tricky.
“So, yes, let’s say that Merck is going to produce vaccine for Pfizer,” Gilbert said. “Do they have manufacturing facilities with the equipment that will allow them to do that? Probably not; they’re going to have to refit. How long is that going to take, when you are refitting manufacturing facilities to manufacture vaccines that are to be used in people? There’s an awful lot of testing. Once you’ve set it up, making sure it works, transferring the technology — it’s not super fast.”
What's it like to work under so much scrutiny?
The last time there was such intense interest in health science was the early years of the AIDS epidemic — four decades ago. It is no exaggeration that billions of people are watching to see how well the vaccines protect, whether they surprise or disappoint.
“We’re struggling against the head winds of the pandemic, trying to do our best,” Pollard said. “And it seems that all the time people are saying, you should have done your shoelaces up a bit tighter. . . . But, of course, it is because people are so distressed about the impact that this virus is having on their lives. And, of course, the one thing that vaccines do is it gives hope. So it’s not surprising that we’re under huge scrutiny, but it is an odd experience whenever you stick your head out the window and realize that everyone is watching.”
The researchers noted that in the past, vaccine development took years. Now vaccines are emerging in record-breaking time — and there’s pressure to go even faster.
“For every scientist, when you start to get data, you check it and you interrogate it and you get somebody else to look at it and you make sure it’s good before you make it public,” Gilbert said. “And we’re being pushed to make things public very early, because people are trying to get leaks and to break stories. And it’s not good for science, and it’s not good for our ability to make a vaccine that’s going to protect people, because then it ends up with a lot of headlines that people remember that were actually based on misinterpretation or, you know, something wrong.”