A conformation-dependent neutralizing monoclonal antibody specifically targeting receptor-binding domain in Middle East respiratory syndrome coronavirus spike protein.
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 could potentially function as a therapeutic antibody for treating and preventing MERS-CoV infections. Additionally, Mersmab1 may facilitate studies of the conformation and antigenicity of MERS-CoV RBD and thus will guide rational design of MERS-CoV subunit vaccines.


OBJECTIVE
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 health care 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.
Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA.
Lanying
L
Du
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
Guangyu
G
Zhao
Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Yang
Y
Yang
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
Hongjie
H
Qiu
Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA.
Lili
L
Wang
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
Zhihua
Z
Kou
Department of Microbiology and Immunology, and Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, Texas, USA.
Xinrong
X
Tao
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
Hong
H
Yu
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
Shihui
S
Sun
Department of Microbiology and Immunology, and Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, Texas, USA.
Chien-Te K
CT
Tseng
Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai, China.
Shibo
S
Jiang
Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota, USA lifang@umn.edu yszhou@bmi.ac.cn.
Fang
F
Li
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China lifang@umn.edu yszhou@bmi.ac.cn.
Yusen
Y
Zhou
D000818:Animals; D057134:Antibodies, Neutralizing / Q000737:chemistry* / Q000494:pharmacology; D000914:Antibodies, Viral / Q000737:chemistry* / Q000494:pharmacology; D003332:Coronaviridae / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D003333:Coronaviridae Infections / Q000201:enzymology / Q000235:genetics / Q000821:virology*; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism; D018604:Epitope Mapping; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D064370:Spike Glycoprotein, Coronavirus / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D011991:Receptors, Virus; D064370:Spike Glycoprotein, Coronavirus; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4