New Antibodies may Neutralize Omicron and Other COVID-19 Variants

Antibodies that neutralize omicron and other COVID-19 variants by targeting areas of the virus spike protein have been identified by an international team of scientists. The findings were published in the journal Nature. By identifying the targets of these “broadly neutralizing” antibodies on the spike protein, it might be possible to design vaccines and antibody treatments that will be effective against not only the omicron variant but other variants that may emerge in the future, said David Veesler, an investigator with the Howard Hughes Medical Institute and associate professor of biochemistry at the University of Washington School of Medicine in Seattle.

The omicron variant has 37 mutations in the spike protein, which it uses to latch onto and invade cells. This is an unusually high number of mutations.

It is thought that these changes explain in part why the variant has been able to spread so rapidly, to infect people who have been vaccinated, and to reinfect those who have previously been infected.

To assess the effect of these mutations, researchers engineered a disabled, nonreplicating virus, called a pseudovirus, to produce spike proteins on its surface, as coronaviruses do.

They then created pseudoviruses that had spike proteins with the omicron mutations and those found on the earliest variants identified in the pandemic.

Researchers first looked to see how well the different versions of the spike protein were able to bind to a protein on the surface of cells, that the virus uses to latch onto and enter the cell. This protein is called the angiotensin-converting enzyme-2 (ACE2) receptor.

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They found the omicron variant spike protein was able to bind 2.4 times better than the spike protein found in the virus isolated at the very beginning of the pandemic.

They also found that the omicron version was able to bind to mouse ACE2 receptors efficiently, suggesting omicron might be able to “ping-pong” between humans and other mammals.

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Researchers then looked at how well antibodies against earlier isolates of the virus protected against the omicron variant. They did this by using antibodies from patients who had previously been infected with earlier versions of the virus, vaccinated against earlier strains of the virus, or had been infected and then vaccinated.

They found that antibodies from people who had been infected by earlier strains and from those who had received one of the six most-used vaccines currently available all had reduced ability to block infection.

Antibodies from people who had previously been infected and those who had received the Sputnik V or Sinopharm vaccines as well as a single dose of Johnson & Johnson had little or no ability to block – or “neutralize” – the omicron variant's entry into cells.

Antibodies from people who had received two doses of the Moderna, Pfizer/BioNTech, and AstraZeneca vaccines retained some neutralizing activity, albeit reduced by 20- to 40-fold, much more than any other variants.

Antibodies from people who had been infected, recovered, and then had two doses of the vaccine also had reduced activity, but the reduction was less, about fivefold, clearly demonstrating that vaccination after infection is useful.

Antibodies from people, in this case, a group of renal dialysis patients, who had received a booster with a third dose of the mRNA vaccines produced by Moderna and Pfizer/BioNTech showed only a 4-fold reduction in neutralizing activity.

The only exception was an antibody called sotrovimab, which had a two- to three-fold reduction of neutralizing activity.

These findings show that antibodies can neutralize via recognition of conserved areas in so many different variants of the COVID-19 and also suggest that designing vaccines and antibody treatments that target these regions could be effective against a broad spectrum of variants that emerge through mutation.



Source-Medindia