Why Antibodies Become Ineffective Against Omicron

The presence of a large number of mutations, and more than 30 on its spike protein renders antibodies ineffective against the Omicron variant of Covid-19, a study shows.

According to peer-reviewed research published in the Journal of Autoimmunity, an unprecedented number of mutations, particularly in the Spike(S) protein of the Omicron variant, have been linked to its high transmissibility and infectivity.

These mutations also allow it to evade pre-existing antibodies, both by infection and vaccination, in the human body, and account for an increased number of reinfections and breakthrough cases, the Jerusalem Post reported.

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Researchers at the University of Missouri set out to collect data on the mutations found in the Omicron variant S protein.

Using complete sequences from the Omicron variant, the team identified a total of 46 signature mutations in the variant, 23 of which were completely unique and had not been identified in any of the earlier variants of the virus. Two of the mutations were first recorded in the Delta or Delta Plus variant.

Of the 46 mutations found, 30 were identified in the S protein while the rest were located elsewhere in the viral cell, according to the report.

In addition, the team used a pre-existing Protein S structure, which would theoretically prevent antibodies from binding to a virus, to assess whether or not Omicron mutations would similarly affect Covid-19’s Protein S, thus rendering the antibodies ineffective.

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The team found that specific mutations create interference on the surface of the virus, preventing antibodies from binding to it, while others lead to a complete loss of interaction between the antibodies and the virus, thus making the antibodies ineffective against the highly mutated variant, the report says.

This suggests that pre-existing immunization (whether from previous vaccination or infection) may no longer be able to provide optimal protection against the Omicron variant, allowing it to bypass antibodies and enter the immune system, the researchers said.

“The purpose of antibodies is to recognize the virus and stop binding, which prevents infection,” said Kamlendra Singh, a professor in the university’s College of Veterinary Medicine.

“However, we found that many mutations of the Omicron variant are located where antibodies are supposed to bind, so we show how the virus continues to evolve in ways that it can potentially evade or evade existing antibodies, and therefore continue to infect so many people,” he added.

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