The SARS-CoV-2 B.1.1.529 (omicron) variant contains 15 mutations in the receptor-binding domain (RBD). How Omicron evades RBD-targeted neutralizing antibodies — requires immediate investigation. Authors [see attached] used high-throughput yeast display screening to determine the profiles of RBD-escaping mutations for 247 human anti-RBD neutralizing antibodies and showed that the neutralizing antibodies can be classified by unsupervised clustering into six epitope groups (A–F) — a grouping that is highly concordant with knowledge-based structural classifications.
Various single mutations of Omicron can impair neutralizing antibodies of different epitope groups: [a] Neutralizing antibodies in groups A–D, the epitopes of which overlap with the ACE2-binding motif, are largely escaped by K417N, G446S, E484A and
Q493R; [b] Antibodies in group E (e.g., S309) and [c] Antibodies in group F (e.g., CR3022), which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but a subset of neutralizing antibodies are still escaped by
G339D, N440K and S371L. Furthermore, Omicron pseudovirus neutralization showed that neutralizing antibodies that sustained single mutations could also be escaped, owing to multiple synergetic mutations on their epitopes.
In total, >85% of the tested neutralizing antibodies were escaped by Omicron. With regard to neutralizing-antibody-based drugs, the neutralization potency of LY-CoV016, LY-CoV555, REGN10933, REGN10987, AZD1061, AZD8895 and BRII-196 was
greatly undermined by Omicron — whereas VIR-7831 and DXP-604 still functioned at a diminished efficacy. Together, these data suggest that infection with Omicron would result in considerable humoral immune evasion, and that neutralizing antibodies targeting the sarbecovirus-conserved-region will remain most effective. Authors’ state that their results “will advance the development of antibody-based drugs and vaccines against Omicron and future variants.”
This is one paper in the 24 Feb issue of Nature; five more papers on this similar topic are published in sequence [see below]. 😊
Nature 24 Feb 2022; 602: 657-664
But also see: pp 654-656, 664-670, 671-675, 676-681 & 682-688