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A recombinant receptor-binding domain of MERS-CoV in trimeric form protects human dipeptidyl peptidase 4 (hDPP4) transgenic mice from MERS-CoV infection.
Virology. 2016 12; 499:375-382.V

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.

Authors+Show Affiliations

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.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.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.Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, TX, USA.Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, TX, USA.Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN, USA.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.Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA. Electronic address: ldu@nybc.org.State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China. Electronic address: yszhou@bmi.ac.cn.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27750111

Citation

Tai, Wanbo, et al. "A Recombinant Receptor-binding Domain of MERS-CoV in Trimeric Form Protects Human Dipeptidyl Peptidase 4 (hDPP4) Transgenic Mice From MERS-CoV Infection." Virology, vol. 499, 2016, pp. 375-382.
Tai W, Zhao G, Sun S, et al. A recombinant receptor-binding domain of MERS-CoV in trimeric form protects human dipeptidyl peptidase 4 (hDPP4) transgenic mice from MERS-CoV infection. Virology. 2016;499:375-382.
Tai, W., Zhao, G., Sun, S., Guo, Y., Wang, Y., Tao, X., Tseng, C. K., Li, F., Jiang, S., Du, L., & Zhou, Y. (2016). A recombinant receptor-binding domain of MERS-CoV in trimeric form protects human dipeptidyl peptidase 4 (hDPP4) transgenic mice from MERS-CoV infection. Virology, 499, 375-382. https://doi.org/10.1016/j.virol.2016.10.005
Tai W, et al. A Recombinant Receptor-binding Domain of MERS-CoV in Trimeric Form Protects Human Dipeptidyl Peptidase 4 (hDPP4) Transgenic Mice From MERS-CoV Infection. Virology. 2016;499:375-382. PubMed PMID: 27750111.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A recombinant receptor-binding domain of MERS-CoV in trimeric form protects human dipeptidyl peptidase 4 (hDPP4) transgenic mice from MERS-CoV infection. AU - Tai,Wanbo, AU - Zhao,Guangyu, AU - Sun,Shihun, AU - Guo,Yan, AU - Wang,Yufei, AU - Tao,Xinrong, AU - Tseng,Chien-Te K, AU - Li,Fang, AU - Jiang,Shibo, AU - Du,Lanying, AU - Zhou,Yusen, Y1 - 2016/10/15/ PY - 2016/07/18/received PY - 2016/10/04/revised PY - 2016/10/06/accepted PY - 2016/10/18/pubmed PY - 2017/6/16/medline PY - 2016/10/18/entrez KW - Foldon trimerization motif KW - MERS KW - MERS-CoV KW - Neutralization KW - Protection KW - Receptor-binding domain KW - Spike protein KW - hDPP4-transgenic mice SP - 375 EP - 382 JF - Virology JO - Virology VL - 499 N2 - 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. SN - 1096-0341 UR - https://www.unboundmedicine.com/medline/citation/27750111/A_recombinant_receptor_binding_domain_of_MERS_CoV_in_trimeric_form_protects_human_dipeptidyl_peptidase_4__hDPP4__transgenic_mice_from_MERS_CoV_infection_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0042-6822(16)30300-2 DB - PRIME DP - Unbound Medicine ER -