tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Patricia L Brown-Augsburger[SUP] 2 [/SUP], Kizzmekia S Corbett[SUP] 3 [/SUP], Kathryn Westendorf[SUP] 4 [/SUP], Julian Davies[SUP] 5 [/SUP], Thomas P Cujec[SUP] 5 [/SUP], Christopher M Wiethoff[SUP] 2 [/SUP], Jamie L Blackbourne[SUP] 2 [/SUP], Beverly A Heinz[SUP] 2 [/SUP], Denisa Foster[SUP] 5 [/SUP], Richard E Higgs[SUP] 2 [/SUP], Deepa Balasubramaniam[SUP] 5 [/SUP], Lingshu Wang[SUP] 3 [/SUP], Yi Zhang[SUP] 3 [/SUP], Eun Sung Yang[SUP] 3 [/SUP], Roza Bidshahri[SUP] 4 [/SUP], Lucas Kraft[SUP] 4 [/SUP], Yuri Hwang[SUP] 4 [/SUP], Stefanie ?entelis[SUP] 4 [/SUP], Kevin R Jepson[SUP] 4 [/SUP], Rodrigo Goya[SUP] 4 [/SUP], Maia A Smith[SUP] 4 [/SUP], David W Collins[SUP] 4 [/SUP], Samuel J Hinshaw[SUP] 4 [/SUP], Sean A Tycho[SUP] 4 [/SUP], Davide Pellacani[SUP] 4 [/SUP], Ping Xiang[SUP] 4 [/SUP], Krithika Muthuraman[SUP] 4 [/SUP], Solmaz Sobhanifar[SUP] 4 [/SUP], Marissa H Piper[SUP] 5 [/SUP], Franz J Triana[SUP] 5 [/SUP], Jorg Hendle[SUP] 5 [/SUP], Anna Pustilnik[SUP] 5 [/SUP], Andrew C Adams[SUP] 2 [/SUP], Shawn J Berens[SUP] 2 [/SUP], Ralph S Baric[SUP] 6 [/SUP], David R Martinez[SUP] 6 [/SUP], Robert W Cross[SUP] 7 [/SUP], Thomas W Geisbert[SUP] 7 [/SUP], Viktoriya Borisevich[SUP] 7 [/SUP], Olubukola Abiona[SUP] 3 [/SUP], Hayley M Belli[SUP] 8 [/SUP], Maren de Vries[SUP] 9 [/SUP], Adil Mohamed[SUP] 9 [/SUP], Meike Dittmann[SUP] 9 [/SUP], Marie I Samanovic[SUP] 10 [/SUP], Mark J Mulligan[SUP] 10 [/SUP], Jory A Goldsmith[SUP] 11 [/SUP], Ching-Lin Hsieh[SUP] 11 [/SUP], Nicole V Johnson[SUP] 11 [/SUP], Daniel Wrapp[SUP] 11 [/SUP], Jason S McLellan[SUP] 11 [/SUP], Bryan C Barnhart[SUP] 4 [/SUP], Barney S Graham[SUP] 3 [/SUP], John R Mascola[SUP] 3 [/SUP], Carl L Hansen[SUP] 4 [/SUP], Ester Falconer[SUP] 12 [/SUP]
Affiliations
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.
. 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[SUP] 1 [/SUP], Patricia L Brown-Augsburger[SUP] 2 [/SUP], Kizzmekia S Corbett[SUP] 3 [/SUP], Kathryn Westendorf[SUP] 4 [/SUP], Julian Davies[SUP] 5 [/SUP], Thomas P Cujec[SUP] 5 [/SUP], Christopher M Wiethoff[SUP] 2 [/SUP], Jamie L Blackbourne[SUP] 2 [/SUP], Beverly A Heinz[SUP] 2 [/SUP], Denisa Foster[SUP] 5 [/SUP], Richard E Higgs[SUP] 2 [/SUP], Deepa Balasubramaniam[SUP] 5 [/SUP], Lingshu Wang[SUP] 3 [/SUP], Yi Zhang[SUP] 3 [/SUP], Eun Sung Yang[SUP] 3 [/SUP], Roza Bidshahri[SUP] 4 [/SUP], Lucas Kraft[SUP] 4 [/SUP], Yuri Hwang[SUP] 4 [/SUP], Stefanie ?entelis[SUP] 4 [/SUP], Kevin R Jepson[SUP] 4 [/SUP], Rodrigo Goya[SUP] 4 [/SUP], Maia A Smith[SUP] 4 [/SUP], David W Collins[SUP] 4 [/SUP], Samuel J Hinshaw[SUP] 4 [/SUP], Sean A Tycho[SUP] 4 [/SUP], Davide Pellacani[SUP] 4 [/SUP], Ping Xiang[SUP] 4 [/SUP], Krithika Muthuraman[SUP] 4 [/SUP], Solmaz Sobhanifar[SUP] 4 [/SUP], Marissa H Piper[SUP] 5 [/SUP], Franz J Triana[SUP] 5 [/SUP], Jorg Hendle[SUP] 5 [/SUP], Anna Pustilnik[SUP] 5 [/SUP], Andrew C Adams[SUP] 2 [/SUP], Shawn J Berens[SUP] 2 [/SUP], Ralph S Baric[SUP] 6 [/SUP], David R Martinez[SUP] 6 [/SUP], Robert W Cross[SUP] 7 [/SUP], Thomas W Geisbert[SUP] 7 [/SUP], Viktoriya Borisevich[SUP] 7 [/SUP], Olubukola Abiona[SUP] 3 [/SUP], Hayley M Belli[SUP] 8 [/SUP], Maren de Vries[SUP] 9 [/SUP], Adil Mohamed[SUP] 9 [/SUP], Meike Dittmann[SUP] 9 [/SUP], Marie I Samanovic[SUP] 10 [/SUP], Mark J Mulligan[SUP] 10 [/SUP], Jory A Goldsmith[SUP] 11 [/SUP], Ching-Lin Hsieh[SUP] 11 [/SUP], Nicole V Johnson[SUP] 11 [/SUP], Daniel Wrapp[SUP] 11 [/SUP], Jason S McLellan[SUP] 11 [/SUP], Bryan C Barnhart[SUP] 4 [/SUP], Barney S Graham[SUP] 3 [/SUP], John R Mascola[SUP] 3 [/SUP], Carl L Hansen[SUP] 4 [/SUP], Ester Falconer[SUP] 12 [/SUP]
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.