In vivo monoclonal antibody efficacy against SARS-CoV-2 variant strains.

Autor: 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 Jr; 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 Jr; 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.
Jazyk: angličtina
Zdroj: Nature [Nature] 2021 Aug; Vol. 596 (7870), pp. 103-108. Date of Electronic Publication: 2021 Jun 21.
DOI: 10.1038/s41586-021-03720-y
Abstrakt: 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-2 1-3 , 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.
(© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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