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Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection

Middle East respiratory syndrome coronavirus (MERS-CoV) is continuously spreading and causing severe and fatal acute respiratory disease in humans. Prophylactic and therapeutic strategies are therefore urgently needed to control MERS-CoV infection. Here, we generated a humanized monoclonal antibody...

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Autores principales: Qiu, Hongjie, Sun, Shihui, Xiao, He, Feng, Jiannan, Guo, Yan, Tai, Wanbo, Wang, Yufei, Du, Lanying, Zhao, Guangyu, Zhou, Yusen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Authors. Published by Elsevier B.V. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109928/
https://www.ncbi.nlm.nih.gov/pubmed/27312105
http://dx.doi.org/10.1016/j.antiviral.2016.06.003
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author Qiu, Hongjie
Sun, Shihui
Xiao, He
Feng, Jiannan
Guo, Yan
Tai, Wanbo
Wang, Yufei
Du, Lanying
Zhao, Guangyu
Zhou, Yusen
author_facet Qiu, Hongjie
Sun, Shihui
Xiao, He
Feng, Jiannan
Guo, Yan
Tai, Wanbo
Wang, Yufei
Du, Lanying
Zhao, Guangyu
Zhou, Yusen
author_sort Qiu, Hongjie
collection PubMed
description Middle East respiratory syndrome coronavirus (MERS-CoV) is continuously spreading and causing severe and fatal acute respiratory disease in humans. Prophylactic and therapeutic strategies are therefore urgently needed to control MERS-CoV infection. Here, we generated a humanized monoclonal antibody (mAb), designated hMS-1, which targeted the MERS-CoV receptor-binding domain (RBD) with high affinity. hMS-1 significantly blocked MERS-CoV RBD binding to its viral receptor, human dipeptidyl peptidase 4 (hDPP4), potently neutralized infection by a prototype MERS-CoV, and effectively cross-neutralized evolved MERS-CoV isolates through recognizing highly conserved RBD epitopes. Notably, single-dose treatment with hMS-1 completely protected hDPP4 transgenic (hDPP4-Tg) mice from lethal infection with MERS-CoV. Taken together, our data suggest that hMS-1 might be developed as an effective immunotherapeutic agent to treat patients infected with MERS-CoV, particularly in emergent cases.
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spelling pubmed-51099282017-08-01 Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection Qiu, Hongjie Sun, Shihui Xiao, He Feng, Jiannan Guo, Yan Tai, Wanbo Wang, Yufei Du, Lanying Zhao, Guangyu Zhou, Yusen Antiviral Res Article Middle East respiratory syndrome coronavirus (MERS-CoV) is continuously spreading and causing severe and fatal acute respiratory disease in humans. Prophylactic and therapeutic strategies are therefore urgently needed to control MERS-CoV infection. Here, we generated a humanized monoclonal antibody (mAb), designated hMS-1, which targeted the MERS-CoV receptor-binding domain (RBD) with high affinity. hMS-1 significantly blocked MERS-CoV RBD binding to its viral receptor, human dipeptidyl peptidase 4 (hDPP4), potently neutralized infection by a prototype MERS-CoV, and effectively cross-neutralized evolved MERS-CoV isolates through recognizing highly conserved RBD epitopes. Notably, single-dose treatment with hMS-1 completely protected hDPP4 transgenic (hDPP4-Tg) mice from lethal infection with MERS-CoV. Taken together, our data suggest that hMS-1 might be developed as an effective immunotherapeutic agent to treat patients infected with MERS-CoV, particularly in emergent cases. The Authors. Published by Elsevier B.V. 2016-08 2016-06-14 /pmc/articles/PMC5109928/ /pubmed/27312105 http://dx.doi.org/10.1016/j.antiviral.2016.06.003 Text en © 2016 The Authors 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
Qiu, Hongjie
Sun, Shihui
Xiao, He
Feng, Jiannan
Guo, Yan
Tai, Wanbo
Wang, Yufei
Du, Lanying
Zhao, Guangyu
Zhou, Yusen
Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection
title Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection
title_full Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection
title_fullStr Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection
title_full_unstemmed Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection
title_short Single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal Middle East respiratory syndrome (MERS)-coronavirus infection
title_sort single-dose treatment with a humanized neutralizing antibody affords full protection of a human transgenic mouse model from lethal middle east respiratory syndrome (mers)-coronavirus infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109928/
https://www.ncbi.nlm.nih.gov/pubmed/27312105
http://dx.doi.org/10.1016/j.antiviral.2016.06.003
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