Science

Antibodies capable of neutralizing the Omicron variant and the following?

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An international team of researchers has identified antibodies that neutralize the Omicron variant, but also earlier strains of SARS-CoV-2. The antibodies target areas of the virus’s Spike protein that are not changed by the mutation, suggesting that they may also be effective against future variants.

End of the year celebrations are always eagerly awaited, no matter where on the planet you live. This is the moment when we meet with the family, the opportunity to take stock of the last twelve months and hope that the following are better.

Everyone was telling themselves that 2021 was going to be a better year than 2020… Even if the Delta variant tries to stay on top of its successor, the Omicron variant was the real star of the end of the year. It’s not a day when we don’t talk about him.

This variant of the virus spreads much faster than older strains. Omicron has 37 mutations in the Spike protein, which it uses to bind to and invade its host’s cells. An unusually high number of mutations. Scientists believe this is one of the reasons this variant spreads so rapidly, whether it infects people who have been vaccinated or re-infects those who have already been vaccinated.

Evaluation of the effects of the mutation.

An international team of researchers published a study on December 23 in the journal Nature in which they claim to have identified antibodies capable of neutralizing not only the Omicron variant, but also older variants.

To do this, they evaluated the effects of the mutation. They then engineered an inactivated (does not multiply) virus similar to coronaviruses with a Spike protein. They then created another pseudovirus that has a specific Spike protein from the Omicron variant, but also from those found since the beginning of the pandemic.

They then examined the extent to which different versions of the Spike proteins were able to bind to the surface protein that the virus uses to bind and enter the host cell. They found that Omicron’s Spike protein binds 2.4 times better than that found in the virus isolated at the start of the pandemic.

Next, the researchers examined how well the antibodies created to tackle the above variants protected against Omicron. Thus, they used antibodies from patients who had already been infected by the previous versions but also from people who had been vaccinated, or infected + vaccinated. It turned out that the antibodies of people infected with earlier versions, as well as those of people vaccinated with one of the six most widely used vaccines today, had reduced abilities to block infection.

Antibodies generated by vaccination are not very effective

Antibodies from people already infected or vaccinated with Sputnik V, Sinopharm, or a single dose from Johnson & Johnson had little or no neutralizing ability to block the entry of Omicron into cells. Those generated in response to the mRNA vaccines from Pfizer / BioNTech, Moderna and AstraZeneca, retained blocking activity but were reduced 20-40-fold (compared to the starting strain). This is much more than for all other variants.

Antibodies from people infected and then vaccinated with two doses have a more effective neutralizing activity. It is also reduced, of course, but only five times. And the antibodies produced by a third dose of the mRNA vaccine in a group of kidney dialysis patients showed only a four-fold reduction in blocking activity. “This shows that a third dose is really helpful against Omicron,” David Veesler, a Howard Hughes Medical Institute investigator and associate professor of biochemistry at the University of Washington School of Medicine in Seattle, said in a statement. However, according to other studies, the effect of a third dose against Omicron would only last 3-4 months.

Four classes of Omicron-resistant antibodies

But then, are all antibodies doomed to Omicron? All of them, no. A small antibody still resists the invader. This is sotrovimab. It loses its blocking activity against the variant, but only by a factor of 2 or 3. And when scientists tested a larger panel of antibodies, generated to fight the above variants, they identified four classes of antibodies that retain its blocking activity. against Omicron.

Antibodies from each of these four classes target one of the four areas of the SARS-CoV-2 Spike protein, also present in a group of related coronaviruses: sarbecoviruses. These sites on the protein may persist because they perform an essential function that it would lose if mutated. These are called “conserved areas”.

“The discovery that antibodies can neutralize, by recognizing conserved areas in different variants, suggests that vaccine design and treatment with antibodies that attack them can be effective against a wide range of variants. This finding tells us that by targeting antibodies that target these highly conserved sites on the Spike protein, there is a way to overcome the ongoing evolution of the virus, ”concludes Professor Veesler.

Nature

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