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Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization.
Cell Host Microbe. 2021 03 10; 29(3):477-488.e4.CH

Abstract

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. However, viral escape mutants could compromise efficacy. To define immune-selected mutations in the S protein, we exposed a VSV-eGFP-SARS-CoV-2-S chimeric virus, in which the VSV glycoprotein is replaced with the S protein, to 19 neutralizing monoclonal antibodies (mAbs) against the receptor-binding domain (RBD) and generated 50 different escape mutants. Each mAb had a unique resistance profile, although many shared residues within an epitope of the RBD. Some variants (e.g., S477N) were resistant to neutralization by multiple mAbs, whereas others (e.g., E484K) escaped neutralization by convalescent sera. Additionally, sequential selection identified mutants that escape neutralization by antibody cocktails. Comparing these antibody-mediated mutations with sequence variation in circulating SARS-CoV-2 revealed substitutions that may attenuate neutralizing immune responses in some humans and thus warrant further investigation.

Authors+Show Affiliations

Department of Molecular Microbiology, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.Department of Medicine, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.Department of Molecular Microbiology, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.Department of Molecular Microbiology, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA; Program in Virology, Harvard Medical School, Boston, MA, USA.Department of Medicine, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA; Department of Pathology & Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.Department of Molecular Microbiology, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.Department of Pathology & Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.Department of Pathology & Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.Department of Genetics, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.Department of Molecular Microbiology, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.Department of Genetics, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.Department of Molecular Microbiology, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA; Department of Pathology & Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.Department of Pathology & Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA.Department of Molecular Microbiology, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA; Department of Medicine, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA; Department of Pathology & Immunology, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA. Electronic address: diamond@wusm.wustl.edu.Department of Molecular Microbiology, School of Medicine, Washington University in St. Louis, St. Louis, MO, USA. Electronic address: spjwhelan@wustl.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33535027

Citation

Liu, Zhuoming, et al. "Identification of SARS-CoV-2 Spike Mutations That Attenuate Monoclonal and Serum Antibody Neutralization." Cell Host & Microbe, vol. 29, no. 3, 2021, pp. 477-488.e4.
Liu Z, VanBlargan LA, Bloyet LM, et al. Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization. Cell Host Microbe. 2021;29(3):477-488.e4.
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). Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization. Cell Host & Microbe, 29(3), 477-e4. https://doi.org/10.1016/j.chom.2021.01.014
Liu Z, et al. Identification of SARS-CoV-2 Spike Mutations That Attenuate Monoclonal and Serum Antibody Neutralization. Cell Host Microbe. 2021 03 10;29(3):477-488.e4. PubMed PMID: 33535027.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of 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 - 2021/01/27/ PY - 2020/10/30/received PY - 2021/01/06/revised PY - 2021/01/22/accepted PY - 2021/2/4/pubmed PY - 2021/3/25/medline PY - 2021/2/3/entrez KW - ACE2 receptor decoys KW - COVID-19 vaccines KW - SARS-CoV-2 escape mutants KW - convalescent sera KW - coronaviruses KW - monoclonal antibodies KW - receptor-binding domain SP - 477 EP - 488.e4 JF - Cell host & microbe JO - Cell Host Microbe VL - 29 IS - 3 N2 - 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. However, viral escape mutants could compromise efficacy. To define immune-selected mutations in the S protein, we exposed a VSV-eGFP-SARS-CoV-2-S chimeric virus, in which the VSV glycoprotein is replaced with the S protein, to 19 neutralizing monoclonal antibodies (mAbs) against the receptor-binding domain (RBD) and generated 50 different escape mutants. Each mAb had a unique resistance profile, although many shared residues within an epitope of the RBD. Some variants (e.g., S477N) were resistant to neutralization by multiple mAbs, whereas others (e.g., E484K) escaped neutralization by convalescent sera. Additionally, sequential selection identified mutants that escape neutralization by antibody cocktails. Comparing these antibody-mediated mutations with sequence variation in circulating SARS-CoV-2 revealed substitutions that may attenuate neutralizing immune responses in some humans and thus warrant further investigation. SN - 1934-6069 UR - https://www.unboundmedicine.com/medline/citation/33535027/Identification_of_SARS_CoV_2_spike_mutations_that_attenuate_monoclonal_and_serum_antibody_neutralization_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1931-3128(21)00044-5 DB - PRIME DP - Unbound Medicine ER -