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Just weeks after the launch of the vaccines to fight Covid-19, researchers are focusing on a potential new class of vaccines to address the threat posed by rapidly spreading mutations.
Dangerous coronavirus variants identified in Africa, Europe and South America line the globe, prompting scientists in the UK and elsewhere to target multiple versions of the pathogen in one shot and possibly fend off other deadly enemies that might emerge.
A variant that appeared in South Africa has already been shown to be able to partially bypass the defenses raised by several vaccines. The country halted the deployment of an AstraZeneca Plc shot because it offered minimal protection against mild to moderate disease caused by the mutant, called B.1.351. With the spread of a virus comes an increased risk of more alarming mutations.
“We cannot be satisfied with having the vaccines we need and it is only a matter of time to end the pandemic – it is not,” said Richard Hatchett, Managing Director of the Coalition for Epidemic Preparedness Innovations, which has worked to accelerate the development of Covid inoculations. “We are in a race against the virus and we need to get ahead.”
Britain quickly purchased huge stocks of Covid vaccines and became the first Western country to approve a vaccine. Now he is looking to catch up with the epidemic and maintain momentum in the next phase of the crisis, a difficult task as the virus rages on.
Blunt optimism
The government last week announced a pact with CureVac NV to combat variants, combining artificial intelligence to predict future mutations with messenger RNA technology that can quickly generate new vaccines. After the end of a once promising partnership with Sichuan Clover Biopharmaceuticals Inc. and separate trial delays with Sanofi, London-based GlaxoSmithKline Plc is also working with CureVac on anti-mutant vaccines.
Meanwhile, countries in the European Union, which have fallen behind the US and UK on vaccination, have raised questions about the bloc’s mutant strategy. At an ambassadorial meeting on Wednesday, countries like Malta and Germany urged the European Commission to ensure contracts with manufacturers cover sufficient lots if booster injections are needed, according to a cable seen by Bloomberg.
The new variants, including the B.1.1.7 line that surfaced in southern England, dampened the optimism that greeted the highly effective mRNA injections from Pfizer Inc. and Moderna Inc. to the end of last year. Companies should be able to quickly rethink their inoculations based on the distinctive spike protein that the coronavirus uses to invade human cells, according to Michael Kinch, a vaccine specialist at the University of Washington in St. Louis. While scientists have the tools to keep pace, other mutations require alternative approaches, he said.
“The bad news with these particular variants, and the reason many of us are nervous, isn’t that the vaccines suddenly won’t work,” Kinch said, “but that they will slowly become obsolete.”
Pfizer, Moderna and Johnson & Johnson said they were starting to develop booster shots or other efforts to boost their vaccines. AstraZeneca and its partner Oxford aim to have a tweaked version suitable for the new variants available in the fall.
Another strategy is to include a variety of antigens, the molecules in the vaccine that elicit an immune response, Kinch said. Although the spike protein has proven to be a good target, other surface proteins in the envelope and membrane of the virus could also be important.
“Almost work done”
“Spike protein-based vaccines are the first to come out,” said Julian Hiscox, coronavirus specialist and president of infection and global health at the University of Liverpool. The next round could add the N protein – or nucleocapsid -, whose job is to bind viral RNA, he said. With the S and N proteins, “it’s almost work,” he says.
Traditional methods that use the virus itself in a weakened or inactivated form and offer a wider choice of potential targets – such as those used by some Chinese developers, including Sinovac Biotech Ltd. – could also play a bigger role, Kinch said.
CEPI, the Oslo-based group that has funded a number of Covid vaccination programs, has set itself a goal of developing “strain changes” within 100 days if necessary, Hatchett said. Pfizer partner BioNTech SE said that if their vaccine was found to be ineffective against a new strain, they could, in theory, produce an updated injection targeting that variant within six weeks.
For years multivalent influenza vaccines targeting three or four versions of the pathogen have provided protection against multiple strains circling the globe. Glaxo and CureVac plan to leverage mRNA technology to develop a product that addresses multiple variants in a single Covid vaccine. If the work is successful, a vaccine could be ready next year.
This could still have a big impact given the number of countries that still do not have access to vaccines, said Thomas Breuer, chief medical officer of Glaxo’s vaccines unit. One of the major suppliers of influenza vaccines, Glaxo is accustomed to making rapid changes to vaccines, he said.
Following partnerships with the UK and Glaxo, CureVac has been approached by other governments, said Mariola Fotin-Mleczek, its chief technology officer.
“The virus is going to mutate again, so we have to reinvest now,” she said.
Some scientists, including a team from the University of Cambridge, are exploring vaccines that could protect against several coronaviruses to prepare for future pandemics. Backed by British funding, the Cambridge group is developing technology that could be connected to any platform to fight multiple variants and other coronaviruses, such as Middle East respiratory syndrome or MERS. They plan to start human trials in the spring.
The pressure is building
“We have to bring in the next generation who will work not only against these variants, but also against the next pandemic,” said Jonathan Heeney, the Cambridge professor leading the study.
Combinations are another avenue that drug makers are pursuing. Oxford is launching a trial of AstraZeneca and Pfizer vaccines to see if two injections of different products work better. Russia is also planning a study combining the Astra vaccine with its injection of Sputnik V.
As the work progresses, the pressure mounts. New strains could make it harder to get enough immunity to control the virus, Hatchett said.
“Every responsible observer is concerned about what we see. We are going to save a lot of time with the vaccines we have, ”he said. “But we also have to be ready.”
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