The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates.

Autor: Jones BE; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA. jones_bryan_edward@lilly.com ester.falconer@abcellera.com., Brown-Augsburger PL; Eli Lilly and Company, Indianapolis, IN 46225, USA., Corbett KS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Westendorf K; AbCellera Biologics Inc., Vancouver, BC V5Y0A1, Canada., Davies J; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA., Cujec TP; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA., Wiethoff CM; Eli Lilly and Company, Indianapolis, IN 46225, USA., Blackbourne JL; Eli Lilly and Company, Indianapolis, IN 46225, USA., Heinz BA; Eli Lilly and Company, Indianapolis, IN 46225, USA., Foster D; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA., Higgs RE; Eli Lilly and Company, Indianapolis, IN 46225, USA., Balasubramaniam D; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA., Wang L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Zhang Y; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Yang ES; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Bidshahri R; AbCellera Biologics Inc., Vancouver, BC V5Y0A1, Canada., Kraft L; AbCellera Biologics Inc., Vancouver, BC V5Y0A1, Canada., Hwang Y; AbCellera Biologics Inc., Vancouver, BC V5Y0A1, Canada., Žentelis S; AbCellera Biologics Inc., Vancouver, BC V5Y0A1, Canada., Jepson KR; AbCellera Biologics Inc., Vancouver, BC V5Y0A1, Canada., Goya R; AbCellera Biologics Inc., Vancouver, BC V5Y0A1, Canada., Smith MA; AbCellera Biologics Inc., Vancouver, BC V5Y0A1, Canada., Collins DW; AbCellera Biologics Inc., Vancouver, BC V5Y0A1, Canada., Hinshaw SJ; AbCellera Biologics Inc., Vancouver, BC V5Y0A1, Canada., Tycho SA; AbCellera Biologics Inc., Vancouver, BC V5Y0A1, Canada., Pellacani D; AbCellera Biologics Inc., Vancouver, BC V5Y0A1, Canada., Xiang P; AbCellera Biologics Inc., Vancouver, BC V5Y0A1, Canada., Muthuraman K; AbCellera Biologics Inc., Vancouver, BC V5Y0A1, Canada., Sobhanifar S; AbCellera Biologics Inc., Vancouver, BC V5Y0A1, Canada., Piper MH; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA., Triana FJ; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA., Hendle J; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA., Pustilnik A; Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA., Adams AC; Eli Lilly and Company, Indianapolis, IN 46225, USA., Berens SJ; Eli Lilly and Company, Indianapolis, IN 46225, USA., Baric RS; University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Martinez DR; University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Cross RW; Galveston National Laboratory and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA., Geisbert TW; Galveston National Laboratory and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA., Borisevich V; Galveston National Laboratory and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA., Abiona O; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Belli HM; Department of Population Health, Division of Biostatistics, New York University Grossman School of Medicine, New York, NY 10016, USA., de Vries M; Department of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA., Mohamed A; Department of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA., Dittmann M; Department of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA., Samanovic MI; NYU Langone Vaccine Center, Department of Medicine, Division of Infectious Diseases and Immunology, New York University Grossman School of Medicine, New York, NY 10016, USA., Mulligan MJ; NYU Langone Vaccine Center, Department of Medicine, Division of Infectious Diseases and Immunology, New York University Grossman School of Medicine, New York, NY 10016, USA., Goldsmith JA; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA., Hsieh CL; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA., Johnson NV; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA., Wrapp D; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA., McLellan JS; Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA., Barnhart BC; AbCellera Biologics Inc., Vancouver, BC V5Y0A1, Canada., Graham BS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Mascola JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Hansen CL; AbCellera Biologics Inc., Vancouver, BC V5Y0A1, Canada., Falconer E; AbCellera Biologics Inc., Vancouver, BC V5Y0A1, Canada. jones_bryan_edward@lilly.com ester.falconer@abcellera.com.
Jazyk: angličtina
Zdroj: Science translational medicine [Sci Transl Med] 2021 May 12; Vol. 13 (593). Date of Electronic Publication: 2021 Apr 05.
DOI: 10.1126/scitranslmed.abf1906
Abstrakt: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a public health threat for which preventive and therapeutic agents are urgently needed. Neutralizing antibodies are a key class of therapeutics that may bridge widespread vaccination campaigns and offer a treatment solution in populations less responsive to vaccination. Here, we report that high-throughput microfluidic screening of antigen-specific B cells led to the identification of LY-CoV555 (also known as bamlanivimab), a potent anti-spike neutralizing antibody from a hospitalized, convalescent patient with coronavirus disease 2019 (COVID-19). Biochemical, structural, and functional characterization of LY-CoV555 revealed high-affinity binding to the receptor-binding domain, angiotensin-converting enzyme 2 binding inhibition, and potent neutralizing activity. A pharmacokinetic study of LY-CoV555 conducted in cynomolgus monkeys demonstrated a mean half-life of 13 days and a clearance of 0.22 ml hour -1 kg -1 , consistent with a typical human therapeutic antibody. In a rhesus macaque challenge model, prophylactic doses as low as 2.5 mg/kg reduced viral replication in the upper and lower respiratory tract in samples collected through study day 6 after viral inoculation. This antibody has entered clinical testing and is being evaluated across a spectrum of COVID-19 indications, including prevention and treatment.
(Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)
Databáze: MEDLINE