Potent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike glycoprotein.
The recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no prophylactic and therapeutic agents specifically against MERS-CoV are currently available. Entry of MERS-CoV into target cells depends on binding of the receptor binding domain (RBD) of the viral envelope spike glycoprotein to the cellular receptor dipeptidyl peptidase 4 (DPP4). We report the isolation and characterization of two potent human RBD-specific neutralizing monoclonal antibodies (MERS-4 and MERS-27) derived from single-chain variable region fragments of a nonimmune human antibody library. MERS-4 and MERS-27 inhibited infection of both pseudotyped and live MERS-CoV with IC50 (half-maximal inhibitory concentration) at nanomolar concentrations. MERS-4 also showed inhibitory activity against syncytia formation mediated by interaction between MERS-CoV spike glycoprotein and DPP4. Combination of MERS-4 and MERS-27 demonstrated a synergistic effect in neutralization against pseudotyped MERS-CoV. Biochemical analysis indicated that MERS-4 and MERS-27 blocked RBD interaction with DPP4 on the cell surface. MERS-4, in particular, bound soluble RBD with an about 45-fold higher affinity than DPP4. Mutagenesis analysis suggested that MERS-4 and MERS-27 recognized distinct regions in RBD. These results suggest that MERS-4 and MERS-27 are RBD-specific potent inhibitors and could serve as promising candidates for prophylactic and therapeutic interventions against MERS-CoV infection.
Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
Liwei
L
Jiang
Nianshuang
N
Wang
Teng
T
Zuo
Xuanling
X
Shi
Kwok-Man Vincent
KM
Poon
Yongkang
Y
Wu
Fei
F
Gao
Danyang
D
Li
Ruoke
R
Wang
Jianying
J
Guo
Lili
L
Fu
Kwok-Yung
KY
Yuen
Bo-Jian
BJ
Zheng
Xinquan
X
Wang
Linqi
L
Zhang
D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000502:physiology; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000502:physiology; D000914:Antibodies, Viral / Q000276:immunology / Q000502:physiology*; D006801:Humans; D020128:Inhibitory Concentration 50; D065207:Middle East Respiratory Syndrome Coronavirus / Q000276:immunology*
D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral