SARS-CoV-2 variant evasion of monoclonal antibodies based on in vitro studies

Cox, M. et al. (2023) SARS-CoV-2 variant evasion of monoclonal antibodies based on in vitro studies. Nature Reviews Microbiology, 21(2), pp. 112-124. (doi: 10.1038/s41579-022-00809-7) (PMID:36307535) (PMCID:PMC9616429)

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Abstract

Monoclonal antibodies (mAbs) offer a treatment option for individuals with severe COVID-19 and are especially important in high-risk individuals where vaccination is not an option. Given the importance of understanding the evolution of resistance to mAbs by SARS-CoV-2, we reviewed the available in vitro neutralization data for mAbs against live variants and viral constructs containing spike mutations of interest. Unfortunately, evasion of mAb-induced protection is being reported with new SARS-CoV-2 variants. The magnitude of neutralization reduction varied greatly among mAb–variant pairs. For example, sotrovimab retained its neutralization capacity against Omicron BA.1 but showed reduced efficacy against BA.2, BA.4 and BA.5, and BA.2.12.1. At present, only bebtelovimab has been reported to retain its efficacy against all SARS-CoV-2 variants considered here. Resistance to mAb neutralization was dominated by the action of epitope single amino acid substitutions in the spike protein. Although not all observed epitope mutations result in increased mAb evasion, amino acid substitutions at non-epitope positions and combinations of mutations also contribute to evasion of neutralization. This Review highlights the implications for the rational design of viral genomic surveillance and factors to consider for the development of novel mAb therapies.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Wright, Mr Derek and Thomson, Professor Emma and Hughes, Dr Joseph and Robertson, Professor David and Willett, Professor Brian and Harvey, Dr William
Authors: Cox, M., Peacock, T. P., Harvey, W. T., Hughes, J., Wright, D. W., Willett, B. J., Thomson, E., Gupta, R. K., Peacock, S. J., Robertson, D. L., and Carabelli, A. M.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Nature Reviews Microbiology
Publisher:Nature Research
ISSN:1740-1526
ISSN (Online):1740-1534
Published Online:28 October 2022
Copyright Holders:Copyright © 2022, Springer Nature Limited
First Published:First published in Nature Reviews Microbiology 21(2):112-124
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172630014Cross-Cutting Programme – Viral Genomics and Bioinformatics (Programme 9)David RobertsonMedical Research Council (MRC)MC_UU_12014/12III - Centre for Virus Research