COVID-19 antibody treatments aren't as effective on variants. Here's why

A new study has found that COVID-19 antibody treatments aren't as effective for new variants due to the evolving mutations of the differing virus strains.

Authors behind the study, which was published Tuesday in peer-reviewed journal Biochemistry, say the findings could be used to better inform the development of vaccines and therapeutics in the fight against emerging coronavirus variants.

University of Colorado Anschutz Medical Campus professor and corresponding author Krishna Mallela says the study can also aid scientists in understanding the properties of current and new variants.

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"Earlier studies, including ours, have focused on explaining the effect of single mutations and not the mechanism underlying the co-evolution of mutations," Mallela said in a press release.

"Our study helps explain the concept of convergent evolution by balancing positive and negative selection pressures."

According to scientists, the study provides the "physical basis" for why currently approved antibody therapeutics are not working in neutralizing recent COVID-19 variants, such as the highly transmissible Omicron variant as well as its subvariants.

"Understanding the mechanisms underlying the antibody escape and the location of mutations in the spike protein will help in developing new antibody therapeutics that will work against new variants by targeting epitopes with minimal mutations or developing broad neutralizing antibodies that target multiple epitopes," Mallela said.

According to the study, researchers found that certain mutations appear multiple times in emerging variants showing what is known as convergent evolution.

Scientists note that one such evolution occurs at three amino acid positions -- K417, E484 and N501 -- in the COVID-19 spike protein's receptor binding domain (RBD). The study reports that nearly half of 4.3 million variant sequences in the GISAID database that contain any of these three mutations have all three occurring together.

When individual mutations are joined, the study says damaging or adverse effects are cancelled out, leading to improved selection of the mutations together.

Researchers examined the physical mechanisms underlying the convergent evolution of these three mutations. According to the study, they looked at the individual and collective effects of these mutations on antibody binding to cell receptors and immune escape, as well as protein stability and expression.

The study found the three RBD mutations perform "very distinct and specific roles" that contribute to them often being found together and improving the "viral fitness" of COVID-19 variants -- how efficiently a virus can pass through its entire life cycle.

According to the study, K417 was found to escape Class 1 antibodies, showing increased stability and expression but decreased binding ability.

E484 was found to escape Class 2 antibodies, however, scientists found it had decreased receptor binding, stability and expression.

The study said N501Y showed increased receptor binding, but also had decreased stability and expression.

When these mutations come together, scientists found that the harmful effects are mitigated due to the presence of "compensatory effects" which correct a loss of viral fitness due to earlier mutations.

The study reports that when these three mutations are found together, they show increased receptor binding, escape both Class 1 and Class 2 antibodies, and present similar stability and expression as the original strain of SARS-CoV-2. This is why treatment geared towards the original virus strain is less effective.

The study's authors say the findings suggest that the collective effect of these mutations is "far more advantageous" for virus fitness than individual mutations. They added that the presence of multiple mutations improves the selection of individual mutations.

"As SARS-CoV-2 has evolved from Alpha to Omicron, more and more mutations are accumulating. We hope that by providing research that understands the role of these mutations, we can help further propel research and the development of new therapies to better combat new variants," Mallela said in the release.