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Virology. 2016 Dec;499:375-382. doi: 10.1016/j.virol.2016.10.005. Epub 2016 Oct 15.

A recombinant receptor-binding domain of MERS-CoV in trimeric form protects human dipeptidyl peptidase 4 (hDPP4) transgenic mice from MERS-CoV infection.

Author information

1
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.
2
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
3
Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, TX, USA.
4
Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN, USA.
5
Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA; Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Basic Medical College and Institute of Medical Microbiology, Fudan University, Shanghai, China. Electronic address: sjiang@nybc.org.
6
Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA. Electronic address: ldu@nybc.org.
7
State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China. Electronic address: yszhou@bmi.ac.cn.

Abstract

Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) was first identified in 2012, and it continues to threaten human health worldwide. No MERS vaccines are licensed for human use, reinforcing the urgency to develop safe and efficacious vaccines to prevent MERS. MERS-CoV spike protein forms a trimer, and its receptor-binding domain (RBD) serves as a vaccine target. Nevertheless, the protective efficacy of RBD in its native trimeric form has never been evaluated. In this study, a trimeric protein, RBD-Fd, was generated by fusing RBD with foldon trimerization motif. It bound strongly to the receptor of MERS-CoV, dipeptidyl peptidase 4 (DPP4), and elicited robust RBD-specific neutralizing antibodies in mice, maintaining long-term neutralizing activity against MERS-CoV infection. RBD-Fd potently protected hDPP4 transgenic mice from lethal MERS-CoV challenge. These results suggest that MERS-CoV RBD in its trimeric form maintains native conformation and induces protective neutralizing antibodies, making it a candidate for further therapeutic development.

KEYWORDS:

Foldon trimerization motif; MERS; MERS-CoV; Neutralization; Protection; Receptor-binding domain; Spike protein; hDPP4-transgenic mice

PMID:
27750111
PMCID:
PMC5167628
DOI:
10.1016/j.virol.2016.10.005
[Indexed for MEDLINE]
Free PMC Article

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