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Sci Transl Med. Potent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike glycoprotein
[Source: Science Translational Medicine, full page: (LINK). Abstract, edited.]
<CITE>Published in Science Translational Medicine Rapid Publication on April 28 2014, Sci. Transl. Med. DOI: 10.1126/scitranslmed.3008140 </CITE>
<CITE></CITE>Research Article
Potent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike glycoprotein
Liwei Jiang<SUP>1</SUP>,*, Nianshuang Wang<SUP>2</SUP>,*, Teng Zuo<SUP>1, 3</SUP>, Xuanling Shi<SUP>1</SUP>, Kwok-Man Vincent Poon<SUP>4</SUP>, Yongkang Wu<SUP>5</SUP>, Fei Gao<SUP>1</SUP>, Danyang Li<SUP>1</SUP>, Ruoke Wang<SUP>1</SUP>, Jianying Guo<SUP>1</SUP>, Lili Fu<SUP>1</SUP>, Kwok-Yung Yuen<SUP>4</SUP>, Bo-Jian Zheng<SUP>4</SUP>,?, Xinquan Wang<SUP>2</SUP>,? and Linqi Zhang<SUP>1</SUP>
<SUP></SUP>
Author Affiliations: <SUP>1</SUP>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing, China <SUP>2</SUP>Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China <SUP>3</SUP>School of Life Sciences, Tsinghua University, Beijing, China <SUP>4</SUP>Department of Microbiology, the University of Hong Kong, Hong Kong, China <SUP>5</SUP>Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
Author Notes: * Liwei Jiang and Nianshuang Wang contributed equally to this work. ?To whom correspondence should be addressed. E-mail: zhanglinqi@tsinghua.edu.cn (L. Z.); xinquanwang@mail.tsinghua.edu.cn (X. W.) bzheng@hkucc.hku.hk (B. -J.Z.)
Abstract
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). Here we report isolation and characterization of two potent human RBD-specific neutralizing monoclonal antibodies (MERS-4 and MERS-27) derived from single-chain variable region fragments (scFvs) of a nonimmune human antibody library. MERS-4 and MERS-27 inhibited infection of both pseudotyped and live MERS-CoV with IC<SUB>50</SUB> 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 approximately 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.
Copyright ? 2014, American Association for the Advancement of Science
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<CITE>Published in Science Translational Medicine Rapid Publication on April 28 2014, Sci. Transl. Med. DOI: 10.1126/scitranslmed.3008140 </CITE>
<CITE></CITE>Research Article
Potent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike glycoprotein
Liwei Jiang<SUP>1</SUP>,*, Nianshuang Wang<SUP>2</SUP>,*, Teng Zuo<SUP>1, 3</SUP>, Xuanling Shi<SUP>1</SUP>, Kwok-Man Vincent Poon<SUP>4</SUP>, Yongkang Wu<SUP>5</SUP>, Fei Gao<SUP>1</SUP>, Danyang Li<SUP>1</SUP>, Ruoke Wang<SUP>1</SUP>, Jianying Guo<SUP>1</SUP>, Lili Fu<SUP>1</SUP>, Kwok-Yung Yuen<SUP>4</SUP>, Bo-Jian Zheng<SUP>4</SUP>,?, Xinquan Wang<SUP>2</SUP>,? and Linqi Zhang<SUP>1</SUP>
<SUP></SUP>
Author Affiliations: <SUP>1</SUP>Comprehensive AIDS Research Center, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing, China <SUP>2</SUP>Ministry of Education Key Laboratory of Protein Science, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, China <SUP>3</SUP>School of Life Sciences, Tsinghua University, Beijing, China <SUP>4</SUP>Department of Microbiology, the University of Hong Kong, Hong Kong, China <SUP>5</SUP>Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China
Author Notes: * Liwei Jiang and Nianshuang Wang contributed equally to this work. ?To whom correspondence should be addressed. E-mail: zhanglinqi@tsinghua.edu.cn (L. Z.); xinquanwang@mail.tsinghua.edu.cn (X. W.) bzheng@hkucc.hku.hk (B. -J.Z.)
Abstract
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). Here we report isolation and characterization of two potent human RBD-specific neutralizing monoclonal antibodies (MERS-4 and MERS-27) derived from single-chain variable region fragments (scFvs) of a nonimmune human antibody library. MERS-4 and MERS-27 inhibited infection of both pseudotyped and live MERS-CoV with IC<SUB>50</SUB> 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 approximately 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.
Copyright ? 2014, American Association for the Advancement of Science
-
------