Ultra-potent Human Neutralizing Antibody Repertoires Against MERS-CoV from A Recovered Patient

Ultra-potent Human Neutralizing Antibody Repertoires Against MERS-CoV from A Recovered Patient Abstract Background The Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory infection with a high (~35%) mortality rate. Neutralizing antibodies targeting the spike of MERS-CoV have been shown to be a therapeutic option for treatment of lethal disease. Methods We describe the germline diversity and neutralizing activity of 13 potent human monoclonal antibodies that target the MERS-CoV spike protein. Biological functions were assessed by live MERS-CoV, pseudotype particle and its variants, and structural basis were also determined by crystallographic analysis. Results Of the 13 mAbs displaying strong neutralizing activity against MERS-CoV, 2 with the IGHV1-69-derived heavy chain (named MERS-GD27 and MERS-GD33) showed the most potent neutralizing activity against pseudotyped and live MERS-CoV in vitro. Mutagenesis analysis suggested that MERS-GD27 and MERS-GD33 recognized distinct regions in S glycoproteins, and the combination of two mAbs demonstrated a synergistic effect in neutralization against pseudotyped MERS-CoV. The structural basis of MERS-GD27 neutralization and recognition revealed its epitope almost completely overlapped with the receptor-binding site. Conclusions Our data provide new insights into the specific antibody repertoires and the molecular determinants of neutralization during natural MERS-CoV infection in humans. This finding supports additional efforts to design and develop novel therapies to combat MERS-CoV infections in humans. MERS-CoV, neutralizing antibody repertoires, human monoclonal antibody, crystallographic analysis © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Infectious Diseases Oxford University Press

Ultra-potent Human Neutralizing Antibody Repertoires Against MERS-CoV from A Recovered Patient

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Publisher
Oxford University Press
Copyright
© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
ISSN
0022-1899
eISSN
1537-6613
D.O.I.
10.1093/infdis/jiy311
Publisher site
See Article on Publisher Site

Abstract

Abstract Background The Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory infection with a high (~35%) mortality rate. Neutralizing antibodies targeting the spike of MERS-CoV have been shown to be a therapeutic option for treatment of lethal disease. Methods We describe the germline diversity and neutralizing activity of 13 potent human monoclonal antibodies that target the MERS-CoV spike protein. Biological functions were assessed by live MERS-CoV, pseudotype particle and its variants, and structural basis were also determined by crystallographic analysis. Results Of the 13 mAbs displaying strong neutralizing activity against MERS-CoV, 2 with the IGHV1-69-derived heavy chain (named MERS-GD27 and MERS-GD33) showed the most potent neutralizing activity against pseudotyped and live MERS-CoV in vitro. Mutagenesis analysis suggested that MERS-GD27 and MERS-GD33 recognized distinct regions in S glycoproteins, and the combination of two mAbs demonstrated a synergistic effect in neutralization against pseudotyped MERS-CoV. The structural basis of MERS-GD27 neutralization and recognition revealed its epitope almost completely overlapped with the receptor-binding site. Conclusions Our data provide new insights into the specific antibody repertoires and the molecular determinants of neutralization during natural MERS-CoV infection in humans. This finding supports additional efforts to design and develop novel therapies to combat MERS-CoV infections in humans. MERS-CoV, neutralizing antibody repertoires, human monoclonal antibody, crystallographic analysis © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

The Journal of Infectious DiseasesOxford University Press

Published: May 28, 2018

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