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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2021
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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. |
format | Online Article Text |
id | pubmed-8284311 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
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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