Omicron Sub-Variants Escape The Immune System

Scientists in the US have found the mechanism which the BA.1 and BA.2 Omicron sub variants use to escape antibodies and spread rapidly, an advance that could lead to new therapeutic targets and help update COVID-19 vaccine formulations.

The researchers found that the two dominant sub-lineages of Omicron have unprecedented numbers of spike protein mutations, with BA.1 having 33 and BA.2 having 29 variations. These mutations are what lead to their increased transmissibility and enhanced ability to evade the immune system, they said.

The yet-to-be-published findings, posted on the preprint repository bioRxiv, reveal previously unknown mechanisms by which the virus avoids being detected by the immune system.

“Being able to pinpoint some ways the BA.1 and BA.2 Omicron variants are able to evade detection by antibodies, making them more contagious than anything before, could lead to new therapeutic targets and help update vaccine formulations,” said Jimmy D Gollihar, from the Houston Methodist Department of Pathology and Genomic Medicine.

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“One of the surprising findings in this study was that many mutations with critical roles in immune escape in previous variants of SARS-CoV-2 do not play the same roles in immune escape in Omicron, and, in some cases, the effects of these mutations are completely reversed,” Gollihar said in a statement.

The researchers noted that the virus also appears to be stabilising itself to allow for more Omicron sub variants mutations to evade our immune systems.

The study is the first to systematically dissect each of the Omicron mutations across the entirety of the spike protein, which the virus uses to enter and infect the cells, they said.

“We developed a comprehensive map showing various mechanisms of immune escape by Omicron that allows us to identify which antibodies retain neutralisation activity against the virus, Gollihar said.

“This and future work will enable clinicians to make informed decisions about the use of monoclonal antibody therapy and aid in the development of next-generation vaccines, he added.

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The researchers said it is possible that the continuing accumulation of mutations may set the stage for greatly altering the equilibrium and stability of the spike protein in a way that allows for new, more virulent strains to develop.

Understanding this evolution is critical to better inform future therapeutic targets and vaccine formulations, as the SARS-CoV-2 virus will continue to evolve with new variants inevitably arising and spreading, they said.

The strategy used in the study also will be applicable to future zoonotic outbreaks and other microbial pathogens, providing a powerful platform for investigating evolutionary trajectories of infectious agents and engineering appropriate and adaptable vaccines, according to the researchers.

“We will continue to monitor the virus for changes in the spike protein and add new antibodies to test as they are discovered. Continuing to do so will allow us to design better probes for antibody discovery in hopes of engineering new therapeutics by finding potent neutralising antibodies across all variants,” Gollihar said. “We have also recently expanded the platform to other pathogens where we hope to stay ahead of other potential outbreaks.

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