Rise of variants sparks push for all-in-one Covid-19 vaccines

By James Paton and Suzi Ring,

Just weeks into the rollout of vaccines to combat Covid-19, researchers are shifting their focus to a new class of potential shots to take on the threat posed by fast-spreading mutations.

Dangerous coronavirus variants identified in Africa, Europe and South America are carpeting the globe, pushing scientists in the U.K. and elsewhere to target multiple versions of the pathogen in a single shot and perhaps head off more lethal foes that may emerge.

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A variant that arose in South Africa has already shown itself capable of partially evading defenses raised by several vaccines. The country paused rolling out a shot from AstraZeneca Plc because it offered minimal protection against mild to moderate illness cause by the mutant, called B.1.351. With a spreading virus comes an increased risk of more alarming mutations.

“We cannot be complacent that we’ve got the vaccines we need and it’s just a matter of time to ending the pandemic -- it’s not,” said Richard Hatchett, chief executive officer of the Coalition for Epidemic Preparedness Innovations, which has worked to accelerate development of Covid inoculations. “We’re in a race with the virus and we’ve got to get ahead of it.”

Britain snapped up huge Covid vaccine supplies early and became the first Western country to approve a shot. Now it’s seeking to catch up with the outbreak and sustain its momentum in the next phase of the crisis, a difficult task as the virus runs rampant.

Blunted Optimism

The government last week announced a pact with CureVac NV to tackle variants, pairing artificial intelligence to predict future mutations with messenger RNA technology that can rapidly generate new vaccines. After a once-promising partnership with Sichuan Clover Biopharmaceuticals Inc. ended and separate trials with Sanofi ran into delays, London-based GlaxoSmithKline Plc is also working with CureVac on mutant-quelling vaccines.

Meanwhile, countries across the European Union, which has lagged the U.S. and U.K. in immunizations, have raised questions about the bloc’s strategy on mutants. At a meeting of ambassadors Wednesday, countries including Malta and Germany urged the European Commission to ensure contracts with manufacturers cover sufficient batches if booster shots are needed, according to a cable seen by Bloomberg.

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The new variants, including the B.1.1.7 lineage that surfaced in southern England, have blunted the optimism that greeted highly-effective mRNA shots from Pfizer Inc. and Moderna Inc. late last year. The companies should be able to quickly redesign their inoculations based on the distinctive spike protein that the coronavirus uses to invade human cells, according to Michael Kinch, a vaccine specialist at Washington University in St. Louis. While scientists have the tools to keep pace, further mutations call for alternative approaches, he said.

“The bad news with these particular variants, and the reason many of us are nervous, isn’t that the vaccines will suddenly not work,” Kinch said, “but that they will slowly become obsolete.”

Pfizer, Moderna and Johnson & Johnson have said they’re starting work on developing booster shots or other efforts to bolster their vaccines. AstraZeneca and partner Oxford aim to have a tweaked version tailored to new variants available by fall.

One problem drugmakers confront in the quest for a single shot that covers different strains is that they don’t yet know which ones will be the most prevalent in the months to come, according to Andrew Pollard, the lead investigator on the Oxford trials.

“We know today which ones you would choose, but the virus is likely to continue to evolve under pressure from human immunity and so that could change over time,” he said.

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Researchers are considering a number of ways to overcome the challenges. Another strategy involves including a variety of antigens, the molecules in the vaccine that provoke an immune response, Kinch said. Although the spike protein has proven to be a good target, other surface proteins in the virus’s envelope and membrane could turn out to be important, too.

‘Almost Job Done’

“Vaccines based on the spike protein are the first out the door,” said Julian Hiscox, a coronavirus specialist and chair of infection and global health at the University of Liverpool. The next round could add the N -- or nucleocapsid -- protein, whose job is to bind viral RNA, he said. With both S and N proteins, “that’s almost job done,” he said.

Traditional methods that use the virus itself in a weakened or inactivated form and provide a broader choice of potential targets -- like those used by some Chinese developers including Sinovac Biotech Ltd. -- could also play a more significant role, Kinch said.

CEPI, the Oslo-based group that has funded a number of Covid vaccine programs, has set a goal of developing “strain changes” within 100 days if needed, Hatchett said. Pfizer’s partner BioNTech SE has said that if their vaccine turns out to be ineffective against a new strain, they could, in theory, produce an updated shot targeting that variant within six weeks.

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For years, multivalent flu vaccines targeting three or four versions of the pathogen have provided protection against multiple strains circling the globe. Glaxo and CureVac plan to rely on mRNA technology to develop a product that addresses multiple variants in one Covid vaccine. If the work is successful, a vaccine could be ready next year.

That could still have a big impact given how many countries lack access to vaccines, said Thomas Breuer, chief medical officer for Glaxo’s vaccines unit. One of the big flu vaccine suppliers, Glaxo is used to altering vaccines quickly, he said.

Following partnerships with the U.K. and Glaxo, CureVac has been approached by other governments, said Mariola Fotin-Mleczek, its chief technology officer.

“The virus will mutate further, and therefore we need to re-invest now,” she said.

Some scientists, including a team at the University of Cambridge, are exploring vaccines that could protect against multiple coronaviruses to prepare for future pandemics. Backed by U.K. funding, the Cambridge group is developing technology that could be plugged into any platform to fight multiple variants and other coronaviruses, such as Middle East respiratory syndrome, or MERS. They’re planning to start human trials in the spring.

Pressure Rises

“We need to bring on the next generation that are going to work against not only these variants, but the next pandemic,” said Jonathan Heeney, the Cambridge professor leading the study.

Combinations are another avenue drugmakers are pursuing. Oxford is launching a trial bringing AstraZeneca and Pfizer vaccines together to determine whether two shots of different products yield better results. Russia also plans a study mixing the Astra vaccine with its Sputnik V shot.

As the work progresses, the pressure is rising. New strains could make it more difficult to achieve a sufficient level of immunity needed to get control of the virus, Hatchett said.

“Every responsible observer is concerned about what we’re seeing. We’re going to get an awful lot of mileage out of the vaccines that we have,” he said. “But we also need to be ready.”