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In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains.
Nature. 2021 Aug; 596(7870):103-108.Nat

Abstract

Rapidly emerging SARS-CoV-2 variants jeopardize antibody-based countermeasures. Although cell culture experiments have demonstrated a loss of potency of several anti-spike neutralizing antibodies against variant strains of SARS-CoV-21-3, the in vivo importance of these results remains uncertain. Here we report the in vitro and in vivo activity of a panel of monoclonal antibodies (mAbs), which correspond to many in advanced clinical development by Vir Biotechnology, AbbVie, AstraZeneca, Regeneron and Lilly, against SARS-CoV-2 variant viruses. Although some individual mAbs showed reduced or abrogated neutralizing activity in cell culture against B.1.351, B.1.1.28, B.1.617.1 and B.1.526 viruses with mutations at residue E484 of the spike protein, low prophylactic doses of mAb combinations protected against infection by many variants in K18-hACE2 transgenic mice, 129S2 immunocompetent mice and hamsters, without the emergence of resistance. Exceptions were LY-CoV555 monotherapy and LY-CoV555 and LY-CoV016 combination therapy, both of which lost all protective activity, and the combination of AbbVie 2B04 and 47D11, which showed a partial loss of activity. When administered after infection, higher doses of several mAb cocktails protected in vivo against viruses with a B.1.351 spike gene. Therefore, many-but not all-of the antibody products with Emergency Use Authorization should retain substantial efficacy against the prevailing variant strains of SARS-CoV-2.

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Authors+Show Affiliations

Chen RE
Department of Medicine, Washington University School of Medicine, St Louis, MO, USA. Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.
Winkler ES
Department of Medicine, Washington University School of Medicine, St Louis, MO, USA. Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.
Case JB
Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
Aziati ID
Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
Bricker TL
Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
Joshi A
Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
Darling TL
Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
Ying B
Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
Errico JM
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.
Shrihari S
Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
VanBlargan LA
Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
Xie X
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
Gilchuk P
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Zost SJ
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Droit L
Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO, USA.
Liu Z
Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO, USA.
Stumpf S
Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO, USA.
Wang D
Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO, USA.
Handley SA
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.
Stine WB
AbbVie Bioresearch Center, Worcester, MA, USA.
Shi PY
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA. Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA. Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX, USA.
Davis-Gardner ME
Center for Childhood Infections and Vaccines of Children's Healthcare of Atlanta, Department of Pediatrics, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
Suthar MS
Center for Childhood Infections and Vaccines of Children's Healthcare of Atlanta, Department of Pediatrics, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
Knight MG
Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA.
Andino R
Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA.
Chiu CY
Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA. Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Ellebedy AH
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA. Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis, MO, USA. Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St Louis, MO, USA.
Fremont DH
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA. Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO, USA. Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO, USA.
Whelan SPJ
Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO, USA.
Crowe JE
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA. Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Purcell L
Vir Biotechnology, St Louis, MO, USA.
Corti D
Humabs BioMed SA, a subsidiary of Vir Biotechnology, Bellinzona, Switzerland.
Boon ACM
Department of Medicine, Washington University School of Medicine, St Louis, MO, USA. Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA. Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO, USA.
Diamond MS
Department of Medicine, Washington University School of Medicine, St Louis, MO, USA. diamond@wusm.wustl.edu. Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA. diamond@wusm.wustl.edu. Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO, USA. diamond@wusm.wustl.edu. Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis, MO, USA. diamond@wusm.wustl.edu. Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St Louis, MO, USA. diamond@wusm.wustl.edu.

MeSH

Angiotensin-Converting Enzyme 2AnimalsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralCOVID-19Chlorocebus aethiopsFemaleHumansMaleMesocricetusMiceMice, TransgenicNeutralization TestsPost-Exposure ProphylaxisPre-Exposure ProphylaxisSARS-CoV-2Serine EndopeptidasesSpike Glycoprotein, CoronavirusVero Cells

Pub Type(s)

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

Language

eng

PubMed ID

34153975

Citation

Chen, Rita E., et al. "In Vivo Monoclonal Antibody Efficacy Against SARS-CoV-2 Variant Strains." Nature, vol. 596, no. 7870, 2021, pp. 103-108.
Chen RE, Winkler ES, Case JB, et al. In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains. Nature. 2021;596(7870):103-108.
Chen, R. E., Winkler, E. S., Case, J. B., Aziati, I. D., Bricker, T. L., Joshi, A., Darling, T. L., Ying, B., Errico, J. M., Shrihari, S., VanBlargan, L. A., Xie, X., Gilchuk, P., Zost, S. J., Droit, L., Liu, Z., Stumpf, S., Wang, D., Handley, S. A., ... Diamond, M. S. (2021). In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains. Nature, 596(7870), 103-108. https://doi.org/10.1038/s41586-021-03720-y
Chen RE, et al. In Vivo Monoclonal Antibody Efficacy Against SARS-CoV-2 Variant Strains. Nature. 2021;596(7870):103-108. PubMed PMID: 34153975.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains. AU - Chen,Rita E, AU - Winkler,Emma S, AU - Case,James Brett, AU - Aziati,Ishmael D, AU - Bricker,Traci L, AU - Joshi,Astha, AU - Darling,Tamarand L, AU - Ying,Baoling, AU - Errico,John M, AU - Shrihari,Swathi, AU - VanBlargan,Laura A, AU - Xie,Xuping, AU - Gilchuk,Pavlo, AU - Zost,Seth J, AU - Droit,Lindsay, AU - Liu,Zhuoming, AU - Stumpf,Spencer, AU - Wang,David, AU - Handley,Scott A, AU - Stine,W Blaine,Jr AU - Shi,Pei-Yong, AU - Davis-Gardner,Meredith E, AU - Suthar,Mehul S, AU - Knight,Miguel Garcia, AU - Andino,Raul, AU - Chiu,Charles Y, AU - Ellebedy,Ali H, AU - Fremont,Daved H, AU - Whelan,Sean P J, AU - Crowe,James E,Jr AU - Purcell,Lisa, AU - Corti,Davide, AU - Boon,Adrianus C M, AU - Diamond,Michael S, Y1 - 2021/06/21/ PY - 2021/4/21/received PY - 2021/6/11/accepted PY - 2021/6/22/pubmed PY - 2021/8/11/medline PY - 2021/6/21/entrez SP - 103 EP - 108 JF - Nature JO - Nature VL - 596 IS - 7870 N2 - Rapidly emerging SARS-CoV-2 variants jeopardize antibody-based countermeasures. Although cell culture experiments have demonstrated a loss of potency of several anti-spike neutralizing antibodies against variant strains of SARS-CoV-21-3, the in vivo importance of these results remains uncertain. Here we report the in vitro and in vivo activity of a panel of monoclonal antibodies (mAbs), which correspond to many in advanced clinical development by Vir Biotechnology, AbbVie, AstraZeneca, Regeneron and Lilly, against SARS-CoV-2 variant viruses. Although some individual mAbs showed reduced or abrogated neutralizing activity in cell culture against B.1.351, B.1.1.28, B.1.617.1 and B.1.526 viruses with mutations at residue E484 of the spike protein, low prophylactic doses of mAb combinations protected against infection by many variants in K18-hACE2 transgenic mice, 129S2 immunocompetent mice and hamsters, without the emergence of resistance. Exceptions were LY-CoV555 monotherapy and LY-CoV555 and LY-CoV016 combination therapy, both of which lost all protective activity, and the combination of AbbVie 2B04 and 47D11, which showed a partial loss of activity. When administered after infection, higher doses of several mAb cocktails protected in vivo against viruses with a B.1.351 spike gene. Therefore, many-but not all-of the antibody products with Emergency Use Authorization should retain substantial efficacy against the prevailing variant strains of SARS-CoV-2. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/34153975/In_vivo_monoclonal_antibody_efficacy_against_SARS_CoV_2_variant_strains_ DB - PRIME DP - Unbound Medicine ER -