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; Žentelis, 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.; Wrapp, Daniel; McLellan, Jason S.; Barnhart, Bryan C.; Graham, Barney S.; Mascola, John R.; Hansen, Carl L.; Falconer, Ester

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.