[Source: Journal of Virology, full page: (LINK). Abstract, edited.]


A Conformation-Dependent Neutralizing Monoclonal Antibody Specifically Targeting Receptor-Binding Domain in MERS-CoV Spike Protein

Lanying Du a, Guangyu Zhao b, Yang Yang c, Hongjie Qiu b, Lili Wang a, Zhihua Kou b, Xinrong Tao d, Hong Yu b, Shihui Sun b, Chien-Te K Tseng d, Shibo Jiang a,e, Fang Li c# and Yusen Zhou b#

Author Affiliations: <SUP>a</SUP>Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA <SUP>b</SUP>State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China <SUP>c</SUP>Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota, USA <SUP>d</SUP>Department of Microbiology and Immunology, and Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, Texas, USA <SUP>e</SUP>Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai, China


ABSTRACT

Prophylactic and therapeutic strategies are urgently needed to combat infections caused by the newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV). Here we have developed a neutralizing monoclonal antibody (mAb), designated Mersmab1, which potently blocks MERS-CoV entry into human cells. Biochemical assays reveal that Mersmab1 specifically binds to the receptor-binding domain (RBD) of the MERS-CoV spike protein, and thereby competitively blocks the binding of the RBD to its cellular receptor dipeptidyl peptidase 4 (DPP4). Furthermore, alanine scanning of the RBD has identified several residues at the DPP4-binding surface that serve as neutralizing epitopes for Mersmab1. These results suggest that if humanized, Mersmab1 can potentially function as a therapeutic antibody for treating and preventing MERS-CoV infections. Additionally, Mersmab1 may facilitate studies on the conformation and antigenicity of MERS-CoV RBD and thus will guide rational design of MERS-CoV subunit vaccines.


IMPORTANCE

MERS coronavirus (MERS-CoV) is spreading in the human population and causing severe respiratory diseases with over 40% fatality. No vaccine is currently available to prevent MERS-CoV infections. Here, we have produced a neutralizing monoclonal antibody with the capacity to effectively block MERS-CoV entry into permissive human cells. If humanized, this antibody may be used as a prophylactic and therapeutic agent against MERS-CoV infections. Specifically, when given to a person (e.g., a patient's family member or a healthcare worker), either before or after exposure to MERS-CoV, the humanized antibody may prevent or inhibit MERS-CoV infection, thereby stopping the spread of MERS-CoV in humans. This antibody can also serve as a useful tool to guide the design of effective MERS-CoV vaccines.


FOOTNOTES

#Correspondence. E-mail: lifang@umn.edu (F. Li); yszhou@bmi.ac.cn (Y. Zhou).

Copyright ? 2014, American Society for Microbiology. All Rights Reserved.


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