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The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates.
Jones, Bryan E; Brown-Augsburger, Patricia L; Corbett, Kizzmekia S; Westendorf, Kathryn; Davies, Julian; Cujec, Thomas P; Wiethoff, Christopher M; Blackbourne, Jamie L; Heinz, Beverly A; Foster, Denisa; Higgs, Richard E; Balasubramaniam, Deepa; Wang, Lingshu; Zhang, Yi; Yang, Eun Sung; Bidshahri, Roza; Kraft, Lucas; Hwang, Yuri; Zentelis, Stefanie; Jepson, Kevin R; Goya, Rodrigo; Smith, Maia A; Collins, David W; Hinshaw, Samuel J; Tycho, Sean A; Pellacani, Davide; Xiang, Ping; Muthuraman, Krithika; Sobhanifar, Solmaz; Piper, Marissa H; Triana, Franz J; Hendle, Jorg; Pustilnik, Anna; Adams, Andrew C; Berens, Shawn J; Baric, Ralph S; Martinez, David R; Cross, Robert W; Geisbert, Thomas W; Borisevich, Viktoriya; Abiona, Olubukola; Belli, Hayley M; de Vries, Maren; Mohamed, Adil; Dittmann, Meike; Samanovic, Marie I; Mulligan, Mark J; Goldsmith, Jory A; Hsieh, Ching-Lin; Johnson, Nicole V.
  • 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.
  • Zentelis 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.
Sci Transl Med ; 13(593)2021 05 12.
Article in English | MEDLINE | ID: covidwho-1255516
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / COVID-19 / Antibodies, Viral Type of study: Experimental Studies / Prognostic study Topics: Vaccines Limits: Animals Language: English Journal subject: Science / Medicine Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / COVID-19 / Antibodies, Viral Type of study: Experimental Studies / Prognostic study Topics: Vaccines Limits: Animals Language: English Journal subject: Science / Medicine Year: 2021 Document Type: Article