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Landscape analysis of escape variants identifies SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization.
bioRxiv. 2021 Jan 11B

Abstract

Although neutralizing antibodies against the SARS-CoV-2 spike (S) protein are a goal of COVID-19 vaccines and have received emergency use authorization as therapeutics, viral escape mutants could compromise their efficacy. To define the immune-selected mutational landscape in S protein, we used a VSV-eGFP-SARS-CoV-2-S chimeric virus and 19 neutralizing monoclonal antibodies (mAbs) against the receptor-binding domain (RBD) to generate 50 different escape mutants. The variants were mapped onto the RBD structure and evaluated for cross-resistance to mAbs and convalescent human sera. Each mAb had a unique resistance profile, although many shared residues within an epitope. Some variants (e.g ., S477N) were resistant to neutralization by multiple mAbs, whereas others (e.g ., E484K) escaped neutralization by convalescent sera, suggesting some humans induce a narrow repertoire of neutralizing antibodies. Comparing the antibody-mediated mutational landscape in S with sequence variation in circulating SARS-CoV-2, we define substitutions that may attenuate neutralizing immune responses in some humans.

Authors

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Pub Type(s)

Preprint

Language

eng

PubMed ID

33442690

Citation

Liu, Zhuoming, et al. "Landscape Analysis of Escape Variants Identifies SARS-CoV-2 Spike Mutations That Attenuate Monoclonal and Serum Antibody Neutralization." BioRxiv : the Preprint Server for Biology, 2021.
Liu Z, VanBlargan LA, Bloyet LM, et al. Landscape analysis of escape variants identifies SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization. bioRxiv. 2021.
Liu, Z., VanBlargan, L. A., Bloyet, L. M., Rothlauf, P. W., Chen, R. E., Stumpf, S., Zhao, H., Errico, J. M., Theel, E. S., Liebeskind, M. J., Alford, B., Buchser, W. J., Ellebedy, A. H., Fremont, D. H., Diamond, M. S., & Whelan, S. P. J. (2021). Landscape analysis of escape variants identifies SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization. BioRxiv : the Preprint Server for Biology. https://doi.org/10.1101/2020.11.06.372037
Liu Z, et al. Landscape Analysis of Escape Variants Identifies SARS-CoV-2 Spike Mutations That Attenuate Monoclonal and Serum Antibody Neutralization. bioRxiv. 2021 Jan 11; PubMed PMID: 33442690.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Landscape analysis of escape variants identifies SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization. AU - Liu,Zhuoming, AU - VanBlargan,Laura A, AU - Bloyet,Louis-Marie, AU - Rothlauf,Paul W, AU - Chen,Rita E, AU - Stumpf,Spencer, AU - Zhao,Haiyan, AU - Errico,John M, AU - Theel,Elitza S, AU - Liebeskind,Mariel J, AU - Alford,Brynn, AU - Buchser,William J, AU - Ellebedy,Ali H, AU - Fremont,Daved H, AU - Diamond,Michael S, AU - Whelan,Sean P J, Y1 - 2021/01/11/ PY - 2021/1/15/pubmed PY - 2021/1/15/medline PY - 2021/1/14/entrez JF - bioRxiv : the preprint server for biology JO - bioRxiv N2 - Although neutralizing antibodies against the SARS-CoV-2 spike (S) protein are a goal of COVID-19 vaccines and have received emergency use authorization as therapeutics, viral escape mutants could compromise their efficacy. To define the immune-selected mutational landscape in S protein, we used a VSV-eGFP-SARS-CoV-2-S chimeric virus and 19 neutralizing monoclonal antibodies (mAbs) against the receptor-binding domain (RBD) to generate 50 different escape mutants. The variants were mapped onto the RBD structure and evaluated for cross-resistance to mAbs and convalescent human sera. Each mAb had a unique resistance profile, although many shared residues within an epitope. Some variants (e.g ., S477N) were resistant to neutralization by multiple mAbs, whereas others (e.g ., E484K) escaped neutralization by convalescent sera, suggesting some humans induce a narrow repertoire of neutralizing antibodies. Comparing the antibody-mediated mutational landscape in S with sequence variation in circulating SARS-CoV-2, we define substitutions that may attenuate neutralizing immune responses in some humans. UR - https://www.unboundmedicine.com/medline/citation/33442690/Landscape_analysis_of_escape_variants_identifies_SARS_CoV_2_spike_mutations_that_attenuate_monoclonal_and_serum_antibody_neutralization_ L2 - https://doi.org/10.1101/2020.11.06.372037 DB - PRIME DP - Unbound Medicine ER -
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