Scientists identify an antibody that blocks Omicron!


This image shows the binding of the spike protein (red) by an antibody (blue)

Source: dreamstime


Scientists have identified antibodies that neutralize Omicron and other variants of coronavirus by targeting areas of the viral project that remain essentially unchanged as the virus mutates. The study, published in the journal Nature, may help design vaccines and antibody treatments that will be effective against not just Omicron but other variants that may emerge in the future.

"This finding tells us that by focusing on antibodies that target these highly conserved sites on the spike protein, there is a way to overcome the virus' continual evolution," said David Veesler, an associate professor at the University of Washington School of Medicine in the US.

Spike Protein Mutations


The Omicron variant has an unusually high number of 37 mutations in the spike protein, which the virus uses to enter and infect human cells. Thus, these changes are thought to partly explain why the variant has been able to spread so rapidly and has been able to infect people who have been vaccinated and reinfect those who have previously been infected.

"The main questions we were trying to answer were: how has this constellation of mutations in the spike protein of the Omicron variant affected its ability to bind to cells and to evade the immune system's antibody responses," Veesler said.

Spike proteins of the Coronavirus

Source: Shutterstock


How were the mutations studied?


To assess the effect of these mutations, the researchers engineered a disabled, non-replicating virus, called a pseudovirus. This pseudovirus would produce the same spike proteins on its surface as coronaviruses. They then created pseudoviruses that had spike proteins with the Omicron mutations and those on the earliest variants identified in the pandemic.


The 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. This protein is used by the virus to latch onto and enter the cell. This protein is known as the angiotensin-converting enzyme-2 (ACE2) receptor.


They found that 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.


"That is not a huge increase but in the SARS outbreak in 2002-2003, mutations in the spike protein that increased affinity were associated with higher transmissibility and infectivity."

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.


How were the antibodies studied?


The researchers 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, or vaccinated against earlier strains of the virus, or had been infected and then vaccinated.


The team 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 available all had a reduced ability to block infection.


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 who had received a booster with a third dose of the mRNA vaccines produced by Moderna and Pfizer showed only a 4-fold reduction in their neutralizing activity.


"This shows that a third dose is really, really helpful against Omicron." - Veesler

The Antibody that blocks Omicron


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


However, when a larger panel of antibodies that have been generated against earlier versions of the virus was tested, the researchers identified four classes of antibodies that retained their ability to neutralize Omicron.


Members of each of these classes target one of four specific areas of the spike protein, which are present in not only SARS-CoV-2 variants but also a group of related coronaviruses, called sarbecoviruses. These sites on the protein may persist because they play an essential function that the protein would lose if they mutated. Such areas are called "conserved."


 

The finding that antibodies are able to neutralize via recognition of conserved areas in so many different variants of the virus suggests that designing vaccines and antibody treatments that target these regions could be effective against a broad spectrum of variants.

5 views0 comments