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Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets

The high case-fatality rate of confirmed MERS-CoV infections underlines the urgent need for an effective treatment to reduce the disease severity and mortality. REGN3051 and REGN3048 are two fully human neutralizing monoclonal antibodies (mAb) against MERS-CoV that reduced virus replication in mice...

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Autores principales: de Wit, Emmie, Feldmann, Friederike, Okumura, Atsushi, Horne, Eva, Haddock, Elaine, Saturday, Greg, Scott, Dana, Erlandson, Karl J., Stahl, Neil, Lipsich, Leah, Kyratsous, Christos A., Feldmann, Heinz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier B.V. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113689/
https://www.ncbi.nlm.nih.gov/pubmed/29885377
http://dx.doi.org/10.1016/j.antiviral.2018.06.006
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author de Wit, Emmie
Feldmann, Friederike
Okumura, Atsushi
Horne, Eva
Haddock, Elaine
Saturday, Greg
Scott, Dana
Erlandson, Karl J.
Stahl, Neil
Lipsich, Leah
Kyratsous, Christos A.
Feldmann, Heinz
author_facet de Wit, Emmie
Feldmann, Friederike
Okumura, Atsushi
Horne, Eva
Haddock, Elaine
Saturday, Greg
Scott, Dana
Erlandson, Karl J.
Stahl, Neil
Lipsich, Leah
Kyratsous, Christos A.
Feldmann, Heinz
author_sort de Wit, Emmie
collection PubMed
description The high case-fatality rate of confirmed MERS-CoV infections underlines the urgent need for an effective treatment to reduce the disease severity and mortality. REGN3051 and REGN3048 are two fully human neutralizing monoclonal antibodies (mAb) against MERS-CoV that reduced virus replication in mice expressing human DPP4 upon prophylactic and therapeutic treatment. Here, we evaluated the prophylactic and therapeutic efficacy of REGN3048 and REGN3051 in the common marmoset model of MERS-CoV infection. Intravenous administration of mAb resulted in high levels of MERS-CoV-neutralizing activity in circulating blood. When animals were treated with mAbs one day before challenge, respiratory disease was less severe and, in animals treated with both REGN3048 and REGN3051, viral loads in the lungs were reduced. However, therapeutic treatment on day one after challenge was less efficacious as it did not prevent the development of severe respiratory disease and all treated animals developed bronchointerstitial pneumonia of similar severity as the control animals. Thus, mAb administration may be more effective in a prophylactic treatment regimen rather than treatment of MERS.
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spelling pubmed-71136892020-04-02 Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets de Wit, Emmie Feldmann, Friederike Okumura, Atsushi Horne, Eva Haddock, Elaine Saturday, Greg Scott, Dana Erlandson, Karl J. Stahl, Neil Lipsich, Leah Kyratsous, Christos A. Feldmann, Heinz Antiviral Res Article The high case-fatality rate of confirmed MERS-CoV infections underlines the urgent need for an effective treatment to reduce the disease severity and mortality. REGN3051 and REGN3048 are two fully human neutralizing monoclonal antibodies (mAb) against MERS-CoV that reduced virus replication in mice expressing human DPP4 upon prophylactic and therapeutic treatment. Here, we evaluated the prophylactic and therapeutic efficacy of REGN3048 and REGN3051 in the common marmoset model of MERS-CoV infection. Intravenous administration of mAb resulted in high levels of MERS-CoV-neutralizing activity in circulating blood. When animals were treated with mAbs one day before challenge, respiratory disease was less severe and, in animals treated with both REGN3048 and REGN3051, viral loads in the lungs were reduced. However, therapeutic treatment on day one after challenge was less efficacious as it did not prevent the development of severe respiratory disease and all treated animals developed bronchointerstitial pneumonia of similar severity as the control animals. Thus, mAb administration may be more effective in a prophylactic treatment regimen rather than treatment of MERS. Elsevier B.V. 2018-08 2018-06-07 /pmc/articles/PMC7113689/ /pubmed/29885377 http://dx.doi.org/10.1016/j.antiviral.2018.06.006 Text en © 2018 Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
de Wit, Emmie
Feldmann, Friederike
Okumura, Atsushi
Horne, Eva
Haddock, Elaine
Saturday, Greg
Scott, Dana
Erlandson, Karl J.
Stahl, Neil
Lipsich, Leah
Kyratsous, Christos A.
Feldmann, Heinz
Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets
title Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets
title_full Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets
title_fullStr Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets
title_full_unstemmed Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets
title_short Prophylactic and therapeutic efficacy of mAb treatment against MERS-CoV in common marmosets
title_sort prophylactic and therapeutic efficacy of mab treatment against mers-cov in common marmosets
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113689/
https://www.ncbi.nlm.nih.gov/pubmed/29885377
http://dx.doi.org/10.1016/j.antiviral.2018.06.006
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