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As vaccines begin to offer hope of an exit from the pandemic, British officials on Saturday sounded an urgent alarm over what they called a highly contagious new variant of the coronavirus circulating in England.
Citing the rapid spread of the virus in and around London, Prime Minister Boris Johnson has imposed the country’s toughest lockdown since March. “When the virus changes its method of attack, we have to change our method of defense,” he said.
In South Africa, a similar version of the virus has emerged, which appears to share some of the mutations seen in the British variant. This virus was found in 90% of samples whose genetic sequences were analyzed in South Africa.
Scientists are worried about these variants but are not surprised by them. Researchers have recorded thousands of tiny changes in the genetic material of the coronavirus as it hopscotched around the world.
Some variants become more common in a population just by luck, not because the changes somehow overload the virus. But as it becomes more difficult for the pathogen to survive – due to vaccinations and the growing immunity of human populations – researchers also expect the virus to obtain useful mutations that allow it to spread more easily. or escape detection by the immune system.
“It’s a real warning that we need to be more careful,” Jesse Bloom, evolutionary biologist at the Fred Hutchinson Cancer Research Center in Seattle. “Certainly these mutations are going to spread and, certainly, the scientific community – we have to watch out for these mutations and we have to characterize those that are having effects.”
The British variant has around 20 mutations, several of which affect how the virus locks onto and infects human cells. These mutations could allow the variant to replicate and transmit more efficiently, said Muge Cevik, an infectious disease expert at the University of St. Andrews in Scotland and science adviser to the UK government.
But the estimate of greater transmissibility – UK officials said the variant was up to 70% more transmissible – is based on modeling and has not been confirmed in laboratory experiments, added Dr Cevik.
“Overall, I think we need a little more experimental data,” she said. “We cannot totally exclude the fact that some of this transmissibility data could be linked to human behavior.”
In South Africa, too, scientists quickly saw that human behavior was driving the epidemic, and not new mutations whose effect on transmissibility had not yet been quantified.
The British announcement also raised concerns that the virus could evolve to become resistant to vaccines being deployed. Concerns are focused on a pair of alterations in the viral genetic code that may make it less vulnerable to certain antibodies.
But several experts have called for caution, saying it would take years – not months – for the virus to evolve enough to render current vaccines powerless.
“No one should worry that there will be just one catastrophic mutation that suddenly renders all immunity and antibodies unnecessary,” Dr Bloom said.
“It will be a process that will occur on a timescale of several years and will require the accumulation of multiple viral mutations,” he added. “It won’t be like an on-off switch.”
Like all viruses, the coronavirus is a shape-shifter. Some genetic changes are harmless, but some can give it an advantage.
Scientists fear the latter possibility, in particular: vaccinating millions of people can put enormous pressure on the virus to become resistant to the immune response, delaying the global fight by several years.
Already, there are small changes in the virus that have appeared independently several times around the world, suggesting that the mutations are useful to the pathogen. The mutation affecting antibody sensitivity – technically referred to as a 69-70 deletion, which means letters are missing in the genetic code – has been observed at least three times: in Danish mink, in the British and in an immunocompromised patient who is became much less sensitive to convalescent plasma.
“This thing transmits, it acquires, it adapts all the time,” said Dr Ravindra Gupta, a virologist at the University of Cambridge, who last week detailed the recurrent emergence and spread of suppression. “But people don’t want to hear what we’re saying, which is this virus is going to mutate.”
The new genetic suppression alters the spike protein on the surface of the coronavirus, which it needs to infect human cells. Variants of the virus with this deletion independently emerged in Thailand and Germany in early 2020 and became widespread in Denmark and England in August.
Scientists initially believed the new coronavirus was stable and likely would not escape the vaccine-induced immune response, said Dr Deepti Gurdasani, clinical epidemiologist at Queen Mary University in London.
“But it has become very clear over the past few months that mutations can occur,” she said. “As the selection pressure increases with mass vaccination, I think these mutants will become more common.”
Several recent papers have shown that the coronavirus can evolve to avoid recognition by a single monoclonal antibody, a cocktail of two antibodies, or even convalescent serum given to a specific individual.
Fortunately, the whole body’s immune system is a much more formidable opponent.
The Pfizer-BioNTech and Moderna vaccines induce an immune response only to the peak protein carried by the coronavirus on its surface. But each infected person produces a large, unique and complex repertoire of antibodies against this protein.
“The point is, you have a thousand big guns pointed at the virus,” said Kartik Chandran, a virologist at Albert Einstein College of Medicine in New York City. “No matter how the virus twists and weaves itself, it’s not that easy to find a genetic solution that can really combat all of these different specifics of antibodies, let alone the other arms of the immune response.
In short: it will be very difficult for the coronavirus to escape the body’s defenses, despite the many variations it can adopt.
To escape immunity, a virus must accumulate a series of mutations, each allowing the pathogen to erode the effectiveness of the body’s defenses. Some viruses, like the flu, make these changes quite quickly. But others, like the measles virus, hardly pick up any of the changes.
Even the influenza virus takes five to seven years to collect enough mutations to entirely evade immune recognition, noted Dr. Bloom. His lab released a new report on Friday showing that common cold coronaviruses also evolve to evade immune detection – but over many years.
The scale of infections in this pandemic could quickly generate diversity in the novel coronavirus. Yet a large majority of people around the world have not yet been infected, which has given scientists hope.
“It would be a bit surprising to me if we saw active selection for immune evasion,” said Emma Hodcroft, molecular epidemiologist at the University of Bern in Switzerland.
“In a population that is still mostly naive, the virus just doesn’t need to do it again,” she said. “But it’s something we want to watch for the long term, especially as we start to vaccinate more people.”
Immunizing about 60% of a population in about a year and reducing the number of cases while that happens will help minimize the chances of significant mutations in the virus, Dr Hodcroft said.
Yet scientists will need to closely monitor the evolution of the virus to spot mutations that could give it an advantage over vaccines.
Scientists regularly monitor influenza virus mutations to update vaccines and should do the same for the coronavirus, said Trevor Bedford, an evolutionary biologist at the Fred Hutchinson Cancer Research Center in Seattle.
“You can imagine a process like the flu shot, where you swap these variants and everyone gets their annual Covid shot,” he said. “I think that’s what will generally be needed.”
The good news is that the technology used in the Pfizer-BioNTech and Moderna vaccines is much easier to adjust and update than conventional vaccines. The new vaccines also generate a massive immune response, so the coronavirus may require many mutations over the years before vaccines need to be changed, Dr Bedford said.
In the meantime, he and other experts said the Centers for Disease Control and Prevention and other government agencies should put in place a national system to link virus sequence databases to data in the field – per example if an infection has occurred despite vaccination.
“These are useful pushes for scientists and governments to put systems in place – now, before we need them, especially when we start vaccinating people,” said Dr Hodcroft. “But the public shouldn’t necessarily panic.”
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