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Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies.
- Source :
-
Nature [Nature] 2022 Feb; Vol. 602 (7898), pp. 657-663. Date of Electronic Publication: 2021 Dec 23. - Publication Year :
- 2022
-
Abstract
- The SARS-CoV-2 B.1.1.529 (Omicron) variant contains 15 mutations of the receptor-binding domain (RBD). How Omicron evades RBD-targeted neutralizing antibodies requires immediate investigation. Here we use high-throughput yeast display screening <superscript>1,2</superscript> to determine the profiles of RBD escaping mutations for 247 human anti-RBD neutralizing antibodies and show 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 <superscript>3-5</superscript> . Various single mutations of Omicron can impair neutralizing antibodies of different epitope groups. Specifically, 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. Antibodies in group E (for example, S309) <superscript>6</superscript> and group F (for example, CR3022) <superscript>7</superscript> , 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, over 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 reduced efficacy. Together, our 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. Our results inform the development of antibody-based drugs and vaccines against Omicron and future variants.<br /> (© 2021. The Author(s).)
- Subjects :
- Angiotensin-Converting Enzyme 2 metabolism
Antibodies, Monoclonal immunology
Antibodies, Monoclonal therapeutic use
Antibodies, Neutralizing classification
Antibodies, Viral classification
COVID-19 immunology
COVID-19 virology
COVID-19 Vaccines immunology
Cells, Cultured
Convalescence
Epitopes, B-Lymphocyte chemistry
Epitopes, B-Lymphocyte immunology
Humans
Immune Sera immunology
Models, Molecular
Mutation
SARS-CoV-2 chemistry
SARS-CoV-2 genetics
Spike Glycoprotein, Coronavirus chemistry
Spike Glycoprotein, Coronavirus genetics
Spike Glycoprotein, Coronavirus immunology
Spike Glycoprotein, Coronavirus metabolism
Antibodies, Neutralizing immunology
Antibodies, Viral immunology
Immune Evasion immunology
Neutralization Tests
SARS-CoV-2 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 602
- Issue :
- 7898
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 35016194
- Full Text :
- https://doi.org/10.1038/s41586-021-04385-3