A novel neutralizing monoclonal antibody targeting the N-terminal domain of the MERS-CoV spike protein

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) has caused fatal infections, some through hospital-acquired transmission, in affected regions since its emergence in 2012. Although the virus is not pandemic among humans, it poses a great threat to public health due to its zoonotic origin. Thus, both preventative and therapeutic countermeasures are urgently needed. In this study, we discovered a panel of neutralizing monoclonal antibodies (mAbs) against MERS-CoV, which mapped to a wide range of regions on the spike (S) protein of the virus. In addition to mAbs with neutralizing epitopes located on the receptor-binding domain, one mAb, 5F9, which binds to the N-terminal domain (NTD) of the MERS-CoV S1 subunit, showed efficient neutralizing activity against the wild-type MERS-CoV strain EMC/2012, with a half maximal inhibitory concentration of 0.2 μg/mL. We concluded that a novel neutralizing epitope for MERS-CoV also resides on the NTD of the S protein, indicating that the NTD might be important during the viral infection process. Our findings have significant implications for further vaccine design and for the development of prophylactic and therapeutic monoclonal immunotherapies against MERS-CoV infection.

Emerging Microbes & Infections (2017) 6, e37; doi:10.1038/emi.2017.18; published online 24 May 2017

Keywords:

• coronavirus
• mAb
• MERS-CoV
• neutralizing
• NTD
• RBD

Acknowledgments

This work was supported by grants from the National Key Research and Development Program of China (2016YFD0500301, 2016YFC1200901, and 2016YFC1200200), the Megaproject for Infectious Disease Research of China (2016ZX10004001-003) and the General Program of National Natural Science Foundation of China 31570162. The funders played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors thank Dr. Jinghua Yan and Dr George F Gao (CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China) for providing reagents (rRBD and rNTD), and Dr Bart L Haagmans and Dr Ron A.M. Fouchier (Department of Viroscience, Erasmus Medical Center, Rotterdam, The Netherlands) for providing the HCoV-EMC/2012 strain.

Supplementary Information for this article can be found on the Emerging Microbes & Infections website (http://www.nature.com/emi)