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 (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.
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
Hongjie
H
Qiu
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
Shihui
S
Sun
Beijing Institute of Basic Medical Sciences, Beijing, China.
He
H
Xiao
Beijing Institute of Basic Medical Sciences, Beijing, China.
Jiannan
J
Feng
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
Yan
Y
Guo
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China; Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
Wanbo
W
Tai
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China; Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
Yufei
Y
Wang
Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
Lanying
L
Du
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China. Electronic address: guangyu0525@163.com.
Guangyu
G
Zhao
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China. Electronic address: yszhou@bmi.ac.cn.
Yusen
Y
Zhou
D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000276:immunology*; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000276:immunology*; D002460:Cell Line; D018352:Coronavirus Infections / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality / Q000821:virology*; D003429:Cross Reactions / Q000276:immunology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D065207:Middle East Respiratory Syndrome Coronavirus / Q000187:drug effects / Q000276:immunology*; D009500:Neutralization Tests; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism
D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D011991:Receptors, Virus; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4
Humanized monoclonal antibody; Lethal infection; MERS-CoV; Protection; Receptor-binding domain; Treatment