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

  • Sci Transl Med. 2021 May 12;13(593):eabf1906. doi: 10.1126/scitranslmed.abf1906.
Bryan E Jones  1 ,  Patricia L Brown-Augsburger  2 ,  Kizzmekia S Corbett  3 ,  Kathryn Westendorf  4 ,  Julian Davies  5 ,  Thomas P Cujec  5 ,  Christopher M Wiethoff  2 ,  Jamie L Blackbourne  2 ,  Beverly A Heinz  2 ,  Denisa Foster  5 ,  Richard E Higgs  2 ,  Deepa Balasubramaniam  5 ,  Lingshu Wang  3 ,  Yi Zhang  3 ,  Eun Sung Yang  3 ,  Roza Bidshahri  4 ,  Lucas Kraft  4 ,  Yuri Hwang  4 ,  Stefanie Žentelis  4 ,  Kevin R Jepson  4 ,  Rodrigo Goya  4 ,  Maia A Smith  4 ,  David W Collins  4 ,  Samuel J Hinshaw  4 ,  Sean A Tycho  4 ,  Davide Pellacani  4 ,  Ping Xiang  4 ,  Krithika Muthuraman  4 ,  Solmaz Sobhanifar  4 ,  Marissa H Piper  5 ,  Franz J Triana  5 ,  Jorg Hendle  5 ,  Anna Pustilnik  5 ,  Andrew C Adams  2 ,  Shawn J Berens  2 ,  Ralph S Baric  6 ,  David R Martinez  6 ,  Robert W Cross  7 ,  Thomas W Geisbert  7 ,  Viktoriya Borisevich  7 ,  Olubukola Abiona  3 ,  Hayley M Belli  8 ,  Maren de Vries  9 ,  Adil Mohamed  9 ,  Meike Dittmann  9 ,  Marie I Samanovic  10 ,  Mark J Mulligan  10 ,  Jory A Goldsmith  11 ,  Ching-Lin Hsieh  11 ,  Nicole V Johnson  11 ,  Daniel Wrapp  11 ,  Jason S McLellan  11 ,  Bryan C Barnhart  4 ,  Barney S Graham  3 ,  John R Mascola  3 ,  Carl L Hansen  4 ,  Ester Falconer  12
Affiliations
  • 1. Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA. [email protected] [email protected].
  • 2. Eli Lilly and Company, Indianapolis, IN 46225, USA.
  • 3. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • 4. AbCellera Biologics Inc., Vancouver, BC V5Y0A1, Canada.
  • 5. Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA.
  • 6. University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • 7. Galveston National Laboratory and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • 8. Department of Population Health, Division of Biostatistics, New York University Grossman School of Medicine, New York, NY 10016, USA.
  • 9. Department of Microbiology, New York University Grossman School of Medicine, New York, NY 10016, USA.
  • 10. 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.
  • 11. Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA.
  • 12. AbCellera Biologics Inc., Vancouver, BC V5Y0A1, Canada. [email protected] [email protected].
PMID: 33820835 DOI: 10.1126/scitranslmed.abf1906
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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