Tweet
Sci Transl Med
. 2021 Apr 5;eabf1906.
doi: 10.1126/scitranslmed.abf1906. Online ahead of print.
The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in non-human primates
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 ?entelis 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
- 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 which may bridge widespread vaccination campaigns and offer a treatment solution in populations less responsive to vaccination. Herein, 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 clearance of 0.22 mL/hr/kg, 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 following viral inoculation. This antibody has entered clinical testing and is being evaluated across a spectrum of COVID-19 indications, including prevention and treatment.