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Three new variants of the fast-spreading virus that causes COVID-19 may evade antibodies that act against the original form that caused the pandemic, new research shows.
With few exceptions, whether the antibodies were produced in response to vaccination or a natural infection, or were purified antibodies intended to be used as drugs, the researchers found that they needed more antibodies to neutralize the new variants.
The findings, from laboratory experiments, suggest that the COVID-19 drugs and vaccines developed so far may become less effective as new variants become dominant, as experts say they inevitably will. The researchers looked at variants from South Africa, the UK, and Brazil.
“We are concerned that people who we would expect to have a protective level of antibodies because they have had or been vaccinated against COVID-19 may not be protected against the new variants,” says lead author Michael S. Diamond, professor of medicine. at Washington University in St. Louis.
“There is a wide variation in the amount of antibodies that a person produces in response to vaccination or a natural infection. Some people produce very high levels and are probably still protected against the new and worrying variants.
“But some people, especially the elderly and immunosuppressed, may not produce such high levels of antibodies. If the level of antibodies needed for protection is multiplied by ten, as our data indicates, they may not have enough. The concern is that the people who need protection the most are the least likely to have it. “
Viruses are always mutating
The virus that causes COVID-19, known as SARS-CoV-2, uses a protein called spike to attach itself to and enter cells. People infected with SARS-CoV-2 generate the most protective antibodies against the spike protein.
Consequently, the spike became the primary target of COVID-19 drug and vaccine developers. All three vaccines that the Food and Drug Administration (FDA) has cleared for emergency use in the US, made by Pfizer / BioNTech, Moderna and Johnson & Johnson, all point to a peak. And the researchers selected potent anti-spike antibodies to develop into antibody-based drugs for COVID-19.
Viruses are always mutating, but for nearly a year the mutations that emerged in SARS-CoV-2 did not threaten this spike-based strategy. Then this winter, fast-spreading variants were spotted in the UK, South Africa, Brazil, and elsewhere. Raising concern, all of the new variants carry multiple mutations in their spike genes, which could decrease the effectiveness of spike-targeted drugs and vaccines now used to prevent or treat COVID-19. The researchers gave the newer variants of most concern the names B.1.1.7 (from the UK), B.1.135 (South Africa) and B.1.1.248, also known as P.1 (Brazil).
To assess whether the new variants could evade the antibodies produced to the original form of the virus, Diamond and her colleagues, including first author Rita E. Chen, a graduate student in Diamond’s lab, tested the antibodies’ ability to neutralize three variants of the virus in the laboratory. .
The researchers tested the variants against antibodies in the blood of people who had recovered from SARS-CoV-2 infection or had received the Pfizer vaccine. They also tested antibodies in the blood of mice, hamsters and monkeys that had received an experimental COVID-19 vaccine, developed at the University of Washington School of Medicine, administered through the nose.
Variant B.1.1.7 (UK) could be neutralized with antibody levels similar to those required to neutralize the parent virus. But the other two variants required 3.5 to 10 times more antibodies for neutralization.
Next, they tested monoclonal antibodies – mass-produced replicas of individual antibodies that are exceptionally good at neutralizing the parent virus. When the researchers tested the new viral variants against a panel of monoclonal antibodies, the results ranged from widely effective to completely ineffective.
Continuous antibody detection
Since each virus variant carried multiple mutations in the spike gene, the researchers created a panel of viruses with unique mutations in order to analyze the effect of each mutation. Most of the variation in antibody efficacy could be attributed to a single amino acid change in the peak protein.
This change, called E484K, was found in variants B.1.135 (South Africa) and B.1.1.248 (Brazil), but not in B.1.1.7 (United Kingdom). Variant B.1.135 is widespread in South Africa, which may explain why one of the vaccines tested in people was less effective in South Africa than in the United States, where the variant is still rare, says Diamond.
“We still don’t know exactly what the consequences of these new variants will be,” says Diamond, also a professor of molecular microbiology and of pathology and immunology. “Antibodies are not the only measure of protection; Other elements of the immune system can compensate for the increased resistance to antibodies. That will be determined over time, epidemiologically, as we see what happens as these variants spread.
“Will we see reinfections? Will we see that vaccines lose efficacy and drug resistance emerge? I hope not. But it is clear that we will have to continually screen the antibodies to make sure they continue to work as new variants emerge and spread, and potentially adjust our antibody and vaccine treatment strategies. “
The study appears in Nature medicine. Additional co-authors are from the University of Texas Medical Branch and Washington University in St. Louis.
Funding came from the National Institutes of Health, the Defense Advanced Research Projects Agency, the Dolly Parton COVID-19 Research Fund at Vanderbilt University, the Helen Hay Whitney Foundation, the Sealy & Smith Foundation, the Kleberg Foundation. , the John S. Dunn Foundation, Amon G. Carter Foundation, Gilson Longenbaugh Foundation, Summerfield Robert Foundation, American College of Gastroenterology, EPA Cephalosporin Early Career and Teaching Fellowship, and Townsend-Jeantet Charitable Trust.
Source: Washington University in St. Louis
