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Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection

Middle East Respiratory Syndrome coronavirus (MERS-CoV) has repeatedly caused outbreaks in the Arabian Peninsula. To date, no approved medical countermeasures (MCM) are available to combat MERS-CoV infections. Several neutralizing human monoclonal antibodies (mAbs), including m336, a germline-like h...

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Autores principales: Agrawal, Anurodh Shankar, Ying, Tianlei, Tao, Xinrong, Garron, Tania, Algaissi, Abdullah, Wang, Yanping, Wang, Lili, Peng, Bi-Hung, Jiang, Shibo, Dimitrov, Dimiter S., Tseng, Chien-Te K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990914/
https://www.ncbi.nlm.nih.gov/pubmed/27538452
http://dx.doi.org/10.1038/srep31629
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author Agrawal, Anurodh Shankar
Ying, Tianlei
Tao, Xinrong
Garron, Tania
Algaissi, Abdullah
Wang, Yanping
Wang, Lili
Peng, Bi-Hung
Jiang, Shibo
Dimitrov, Dimiter S.
Tseng, Chien-Te K.
author_facet Agrawal, Anurodh Shankar
Ying, Tianlei
Tao, Xinrong
Garron, Tania
Algaissi, Abdullah
Wang, Yanping
Wang, Lili
Peng, Bi-Hung
Jiang, Shibo
Dimitrov, Dimiter S.
Tseng, Chien-Te K.
author_sort Agrawal, Anurodh Shankar
collection PubMed
description Middle East Respiratory Syndrome coronavirus (MERS-CoV) has repeatedly caused outbreaks in the Arabian Peninsula. To date, no approved medical countermeasures (MCM) are available to combat MERS-CoV infections. Several neutralizing human monoclonal antibodies (mAbs), including m336, a germline-like human mAb, have been chosen as promising MCM for MERS-CoV. However, their clinical development has been hindered by the lack of a robust animal model that recapitulate the morbidity and mortality of human infections. We assessed the prophylactic and therapeutic efficacy of m336 by using well-characterized transgenic mice shown to be highly sensitive to MERS-CoV infection and disease. We found that mice treated with m336 prior to or post lethal MERS-CoV challenging were fully protected, compared to control mice which sufferered from profound weight loss and uniform death within days after infection. Taken together, these results support further development of m336 and other human monoclonal antibodies as potential therapeutics for MERS-CoV infection.
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spelling pubmed-49909142016-08-30 Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection Agrawal, Anurodh Shankar Ying, Tianlei Tao, Xinrong Garron, Tania Algaissi, Abdullah Wang, Yanping Wang, Lili Peng, Bi-Hung Jiang, Shibo Dimitrov, Dimiter S. Tseng, Chien-Te K. Sci Rep Article Middle East Respiratory Syndrome coronavirus (MERS-CoV) has repeatedly caused outbreaks in the Arabian Peninsula. To date, no approved medical countermeasures (MCM) are available to combat MERS-CoV infections. Several neutralizing human monoclonal antibodies (mAbs), including m336, a germline-like human mAb, have been chosen as promising MCM for MERS-CoV. However, their clinical development has been hindered by the lack of a robust animal model that recapitulate the morbidity and mortality of human infections. We assessed the prophylactic and therapeutic efficacy of m336 by using well-characterized transgenic mice shown to be highly sensitive to MERS-CoV infection and disease. We found that mice treated with m336 prior to or post lethal MERS-CoV challenging were fully protected, compared to control mice which sufferered from profound weight loss and uniform death within days after infection. Taken together, these results support further development of m336 and other human monoclonal antibodies as potential therapeutics for MERS-CoV infection. Nature Publishing Group 2016-08-19 /pmc/articles/PMC4990914/ /pubmed/27538452 http://dx.doi.org/10.1038/srep31629 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Agrawal, Anurodh Shankar
Ying, Tianlei
Tao, Xinrong
Garron, Tania
Algaissi, Abdullah
Wang, Yanping
Wang, Lili
Peng, Bi-Hung
Jiang, Shibo
Dimitrov, Dimiter S.
Tseng, Chien-Te K.
Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection
title Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection
title_full Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection
title_fullStr Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection
title_full_unstemmed Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection
title_short Passive Transfer of A Germline-like Neutralizing Human Monoclonal Antibody Protects Transgenic Mice Against Lethal Middle East Respiratory Syndrome Coronavirus Infection
title_sort passive transfer of a germline-like neutralizing human monoclonal antibody protects transgenic mice against lethal middle east respiratory syndrome coronavirus infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990914/
https://www.ncbi.nlm.nih.gov/pubmed/27538452
http://dx.doi.org/10.1038/srep31629
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