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

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; Ester Falconer

doi:10.1126/scitranslmed.abf1906

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

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. JepsonRodrigo 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, Ester Falconer

Research output: Contribution to journal › Article › peer-review

310 Scopus citations

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.

Original language	English (US)
Article number	eabf1906
Journal	Science Translational Medicine
Volume	13
Issue number	593
DOIs	https://doi.org/10.1126/scitranslmed.abf1906
State	Published - May 12 2021
Externally published	Yes

ASJC Scopus subject areas

General Medicine

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10.1126/scitranslmed.abf1906

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Jones, B. E., Brown-Augsburger, P. L., Corbett, K. S., Westendorf, K., Davies, J., Cujec, T. P., Wiethoff, C. M., Blackbourne, J. L., Heinz, B. A., Foster, D., Higgs, R. E., Balasubramaniam, D., Wang, L., Zhang, Y., Yang, E. S., Bidshahri, R., Kraft, L., Hwang, Y., Žentelis, S., ... Falconer, E. (2021). The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates. Science Translational Medicine, 13(593), Article eabf1906. https://doi.org/10.1126/scitranslmed.abf1906

Jones, BE, Brown-Augsburger, PL, Corbett, KS, Westendorf, K, Davies, J, Cujec, TP, Wiethoff, CM, Blackbourne, JL, Heinz, BA, Foster, D, Higgs, RE, Balasubramaniam, D, Wang, L, Zhang, Y, Yang, ES, Bidshahri, R, Kraft, L, Hwang, Y, Žentelis, S, Jepson, KR, Goya, R, Smith, MA, Collins, DW, Hinshaw, SJ, Tycho, SA, Pellacani, D, Xiang, P, Muthuraman, K, Sobhanifar, S, Piper, MH, Triana, FJ, Hendle, J, Pustilnik, A, Adams, AC, Berens, SJ, Baric, RS, Martinez, DR, Cross, RW , Geisbert, TW, Borisevich, V, Abiona, O, Belli, HM, de Vries, M, Mohamed, A, Dittmann, M, Samanovic, MI, Mulligan, MJ, Goldsmith, JA, Hsieh, CL, Johnson, NV, Wrapp, D, McLellan, JS, Barnhart, BC, Graham, BS, Mascola, JR, Hansen, CL & Falconer, E 2021, 'The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates', Science Translational Medicine, vol. 13, no. 593, eabf1906. https://doi.org/10.1126/scitranslmed.abf1906

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

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.",

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

note = "Publisher Copyright: Copyright {\textcopyright} 2021 The Authors, some rights reserved;",

year = "2021",

month = may,

day = "12",

doi = "10.1126/scitranslmed.abf1906",

language = "English (US)",

volume = "13",

journal = "Science Translational Medicine",

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publisher = "American Association for the Advancement of Science",

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T1 - The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates

AU - Jones, Bryan E.

AU - Brown-Augsburger, Patricia L.

AU - Corbett, Kizzmekia S.

AU - Westendorf, Kathryn

AU - Davies, Julian

AU - Cujec, Thomas P.

AU - Wiethoff, Christopher M.

AU - Blackbourne, Jamie L.

AU - Heinz, Beverly A.

AU - Foster, Denisa

AU - Higgs, Richard E.

AU - Balasubramaniam, Deepa

AU - Wang, Lingshu

AU - Zhang, Yi

AU - Yang, Eun Sung

AU - Bidshahri, Roza

AU - Kraft, Lucas

AU - Hwang, Yuri

AU - Žentelis, Stefanie

AU - Jepson, Kevin R.

AU - Goya, Rodrigo

AU - Smith, Maia A.

AU - Collins, David W.

AU - Hinshaw, Samuel J.

AU - Tycho, Sean A.

AU - Pellacani, Davide

AU - Xiang, Ping

AU - Muthuraman, Krithika

AU - Sobhanifar, Solmaz

AU - Piper, Marissa H.

AU - Triana, Franz J.

AU - Hendle, Jorg

AU - Pustilnik, Anna

AU - Adams, Andrew C.

AU - Berens, Shawn J.

AU - Baric, Ralph S.

AU - Martinez, David R.

AU - Cross, Robert W.

AU - Geisbert, Thomas W.

AU - Borisevich, Viktoriya

AU - Abiona, Olubukola

AU - Belli, Hayley M.

AU - de Vries, Maren

AU - Mohamed, Adil

AU - Dittmann, Meike

AU - Samanovic, Marie I.

AU - Mulligan, Mark J.

AU - Goldsmith, Jory A.

AU - Hsieh, Ching Lin

AU - Johnson, Nicole V.

AU - Wrapp, Daniel

AU - McLellan, Jason S.

AU - Barnhart, Bryan C.

AU - Graham, Barney S.

AU - Mascola, John R.

AU - Hansen, Carl L.

AU - Falconer, Ester

PY - 2021/5/12

Y1 - 2021/5/12

N2 - 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.

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

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