Ómicron is a very contagious variant of the coronavirus due to its ability to evade the body’s natural defenses and the protection generated by vaccines, something known as immune escape and which had already been observed in the case of the delta variant. Now, scientists at Washington University School of Medicine in St. Louis, Missouri, have led a study testing five combinations of human monoclonal antibodies used to treat COVID-19 to determine the efficacy of these drugs against ómicron.
Combinations tested in the lab include antibodies discovered at Vanderbilt University Medical Center (VUMC) that were further optimized by AstraZeneca, Evusheld. It is the combination of the antibodies tixagevimab and cilgavimab, whose emergency use has recently been authorized by the United States Food and Drug Administration (FDA) to prevent severe COVID-19.
The researchers found that some antibodies, including those in clinical use from Celltrion, Regeneron and Eli Lilly, completely lost the ability to neutralize the omicron variant in cell culture. In other cases, as occurred with the antibodies discovered at VUMC, their neutralization capacity was observed to be reduced, while the activity of an antibody developed by GlaxoSmithKline (GSK) and Vir Biotechnology –sotrovimab– was minimally affected.
“We still have at least one antibody drug that we can use for each of the indications, prevention or therapy”
“Omicron escapes recognition by many of the monoclonal antibodies used for therapy,” said Dr. James Crowe Jr., director of the Vanderbilt Vaccine Center, whose team discovered the monoclonal antibodies that gave rise to Evusheld. However, according to this expert, the sotrovimab precursor antibody “and the prophylaxis antibodies in Evusheld retain substantial, albeit reduced, activity.”
Which “is good news, as we still have at least one antibody drug that we can use for each of the indications, prevention or therapy.”
Loss of efficacy associated with mutations in the spike protein
The loss of the SARS-CoV-2 neutralization capacity by the monoclonal antibodies evaluated in the study, the results of which have been published in Nature Medicine, is due to the more than 30 mutations in the spike protein that the omicron variant presents , since this protein found on the surface of the virus is the target to which the antibodies are directed.
The decreased inhibitory activity found in this new research is consistent with the observation that antibody responses generated after vaccination or natural infection also lose significant inhibitory activity against omicron, which may help explain why there has been a large increase in symptomatic infections caused by this variant in people who had previously completed their vaccination schedule.
According to the authors of the work – which has been led by Dr. Michael Diamond, a renowned expert in viral pathogenesis at the University of Washington School of Medicine – it is essential to identify and use broad and potent neutralizing monoclonal antibodies that target the areas of the spike protein that are more conserved and less likely to mutate to protect the population against omicron and other variants that may appear in the future.
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