How Omicron Evades Natural Immunity, Vaccination, And Monoclonal Antibody Treatments

This is the third in our series on the Omicron variant. Find parts one and two here.

In a few short weeks, the COVID-19 virus variant Omicron has spread around the world. The incidence of new infections is rising rapidly, even in well-vaccinated populations and those previously infected by earlier variants of SARS-CoV-2. The epidemiologic evidence strongly points to a variant that is resistant to most if not all extant vaccines, and possibly many monoclonal antibodies treatments. Here we explore these concerns. This is the third in our series that outlines what we know about Omicron. We summarize the finding of recent experiments by Cameroni et al. in a bioRxiv preprint from December 14th.

Omicron ACE2 Binding

The first question asked was how tightly the Omicron Spike (S) protein binds to the ACE2 receptor. The data is summarized in Figure 1. Cameroni et al. show that Omicron’s affinity for the ACE2 receptor is 2.5 times as great as that of the S protein from the original Wuhan isolate. Omicron binds to the receptor as well as the Beta variant, but not as well as Alpha, which binds ACE2 almost six times more tightly. The N501Y mutation in Omicron is universally observed to increase affinity roughly 6-fold, yet other mutations in key sites like K417N, Q493R, and G496S were shown by deep mutational scanning to decrease affinity. Increased affinity for the receptor may account, in part, for increased transmissibility, but that is clearly not the whole story as Omicron is much more transmissible than any previously isolates, including Alpha, Beta, Gamma, and Delta.

Read the full article on Forbes.

© William A. Haseltine, PhD. All Rights Reserved.