• Bryan E Jones, Patricia L Brown-Augsburger, Kizzmekia S Corbett, Kathryn Westendorf, Julian Davies, Thomas P Cujec, Christopher M Wiethoff, Jamie L Blackbourne, Beverly A Heinz, Denisa Foster, Richard E Higgs, Deepa Balasubramaniam, Lingshu Wang, Yi Zhang, Eun Sung Yang, Roza Bidshahri, Lucas Kraft, Yuri Hwang, Stefanie Žentelis, Kevin R Jepson, Rodrigo Goya, Maia A Smith, David W Collins, Samuel J Hinshaw, Sean A Tycho, Davide Pellacani, Ping Xiang, Krithika Muthuraman, Solmaz Sobhanifar, Marissa H Piper, Franz J Triana, Jorg Hendle, Anna Pustilnik, Andrew C Adams, Shawn J Berens, Ralph S Baric, David R Martinez, Robert W Cross, Thomas W Geisbert, Viktoriya Borisevich, Olubukola Abiona, Hayley M Belli, Maren de Vries, Adil Mohamed, Meike Dittmann, Marie I Samanovic, Mark J Mulligan, Jory A Goldsmith, Ching-Lin Hsieh, Nicole V Johnson, Daniel Wrapp, Jason S McLellan, Bryan C Barnhart, Barney S Graham, John R Mascola, Carl L Hansen, and Ester Falconer.
• Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA 92121, USA. jones_bryan_edward@lilly.com ester.falconer@abcellera.com.
• Sci Transl Med. 2021 May 12; 13 (593).

AbstractSevere 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).

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