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

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 popula...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284311/
https://www.ncbi.nlm.nih.gov/pubmed/33820835
http://dx.doi.org/10.1126/scitranslmed.abf1906
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author 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
author_facet 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
author_sort Jones, Bryan E.
collection PubMed
description 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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spelling pubmed-82843112021-07-20 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 Sci Transl Med Research Articles 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. American Association for the Advancement of Science 2021-05-12 2021-04-05 /pmc/articles/PMC8284311/ /pubmed/33820835 http://dx.doi.org/10.1126/scitranslmed.abf1906 Text en 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). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
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
The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates
title The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates
title_full The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates
title_fullStr The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates
title_full_unstemmed The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates
title_short The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates
title_sort neutralizing antibody, ly-cov555, protects against sars-cov-2 infection in nonhuman primates
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284311/
https://www.ncbi.nlm.nih.gov/pubmed/33820835
http://dx.doi.org/10.1126/scitranslmed.abf1906
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