Trailing the First Vaccines, Next Generation Turns to Variants

The rapid rollout of vaccines from front-runners includingPfizer Inc. is forcing those trailing behind to shift their focus to fighting potentially more dangerous versions of the coronavirus and find other ways to deploy their technologies.

Imperial College London is unlikely to go ahead with a late-stage trial in the U.K. to test its experimental Covid-19 shot, now that three vaccines have been approved in the country, according toRobin Shattock, the professor leading the research. Instead, his team will aim to provide a boost to first-generation shots, protect people against new variants and combat future threats, he said.

Imperial is changing the strategy after Merck & Co.said Monday it’s abandoning development of two experimental Covid vaccines due to lackluster test results. Imperial has also been seen as a promising contender in the race, but is competing with big companies such as Pfizer,Moderna Inc. and University of Oxford partnerAstraZeneca Plc that have access to significant funding and already crossed the finish line.

“There’s a dilemma,” Shattock said. “People see our approach has very high value for the future, but not necessarily for today.”

Backing Needed

The U.K. university is working with novel messenger RNA technology, as are Pfizer and Moderna, but with a self-amplifying feature aimed at inducing immunity with a much smaller dose. The team would consider carrying out a large international trial elsewhere if it can gain backing from a group such as the Coalition for Epidemic Preparedness Innovations, and expects to make a decision on such a study by March, he said.

Despite key philanthropic and government support, “it’s been impossible to move at the same speed” as the big players, he said.

Imperial had planned to begin larger trials by the end of 2020, targeting potential approval by the middle of this year. Now it will turn to providing annual booster doses that may be needed for shots made by other developers. The team will also work toward driving down costs for making vaccines and developing mRNA technology that could allow long-term storage in refrigerators, rather than the ultra-low temperatures required by some shots.

Targeting Variants

Imperial will also target new variants of the virus, though the developers that have already received approvals will likely have an advantage in adapting their existing vaccines, he said. Moderna said Monday that its vaccine willprotect against two known variants and it plans human studies of a booster shot that might help thwart a strain first identified in South Africa.

Variants that surfaced in the U.K., South Africa and Brazil appear to spread significantly faster than earlier versions and have heightened urgency in the quest to immunize billions of people. While scientists believe that the first-mover vaccines will maintain their effectiveness, some see a risk that the virus could gain an edge over time, developing mutations that could evade that protection.

Scores of vaccine designers around the world are still advancing with experimental shots in various stages of testing. More of them now are focusing on targeting different parts of the virus or trying to protect against multiple variants, Charlie Weller, head of vaccines at U.K.-based health research foundation Wellcome, said in an interview.

“There is a real risk of those variants moving away from the targets we have with the current vaccines,” she said. “The variants are one aspect of why we need different platforms. We still need to invest in other approaches.”

Gap Forming

As countries around the world, mainly wealthy ones, roll out vaccines, a gap is forming between the first and second waves of shots. WhileJohnson & Johnson and Novavax Inc. may deliver vaccine results soon, others have fallen behind. Sanofi andGlaxoSmithKline Plc in December delayed advanced trials of their experimental shot after it failed to produce a sufficient response in older people, pushing its potential availability to the end of this year.

While early studies showed the Imperial vaccine is safe and generates an immune response, it’s difficult to say how it compares with others, Shattock said. With so many receiving approved vaccines in the U.K., it makes it hard to carry out tests, and “it wouldn’t be appropriate to get in the way,” he said.

“We probably will see a slowing down of candidates coming through, because there will be less incentive,” Shattock said. The question is whether to increase the supply of vaccines already known to work or develop a number of new ones, he said. “Where the sweet spot is, is difficult to know right now.”

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