A truncated receptor-binding domain of MERS-CoV spike protein potently inhibits MERS-CoV infection and induces strong neutralizing antibody responses: implication for developing therapeutics and vaccines

• Published in: PloS one Vol. 8; no. 12; p. e81587
• Main Authors: Du, Lanying, Kou, Zhihua, Ma, Cuiqing, Tao, Xinrong, Wang, Lili, Zhao, Guangyu, Chen, Yaoqing, Yu, Fei, Tseng, Chien-Te K, Zhou, Yusen, Jiang, Shibo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 04-12-2013; Public Library of Science (PLoS)
• Subjects: Amino acids; Animals; Antibodies; Antibodies, Neutralizing - immunology; Antibody Formation - immunology; Antibody Specificity - immunology; Binding; Cell culture; Coronaviridae; Coronavirus - physiology; Coronaviruses; Crystallography, X-Ray; Dipeptidyl-peptidase IV; Drug development; Enzymes; Epidemiology; Fc receptors; Female; Health aspects; HIV; Human immunodeficiency virus; Humans; Immune Sera - immunology; Immunoglobulin G; Immunoglobulin G - metabolism; Immunoglobulins; Immunology; Immunotherapy; Infections; Infectious diseases; Laboratories; Mice; Mice, Inbred BALB C; Middle East respiratory syndrome; Peptidase; Protein binding; Protein Structure, Tertiary; Proteins; Public health; Receptors, Fc - metabolism; Recombinant; Recombinant proteins; Recombinant Proteins - immunology; Residues; Respiratory diseases; Respiratory Tract Infections - drug therapy; Respiratory Tract Infections - immunology; Respiratory Tract Infections - virology; Spike Glycoprotein, Coronavirus - metabolism; Spike protein; T cells; Vaccination; Vaccines; Vaccines - immunology; Viral Vaccines - immunology; Viral Vaccines - therapeutic use; Virology; Beijing China; New York; United States > US; Texas; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0081587

An emerging respiratory infectious disease with high mortality, Middle East respiratory syndrome (MERS), is caused by a novel coronavirus (MERS-CoV). It was first reported in 2012 in Saudi Arabia and has now spread to eight countries. Development of effective therapeutics and vaccines is crucial to save lives and halt the spread of MERS-CoV. Here, we show that a recombinant protein containing a 212-amino acid fragment (residues 377-588) in the truncated receptor-binding domain (RBD: residues 367-606) of MERS-CoV spike (S) protein fused with human IgG Fc fragment (S377-588-Fc) is highly expressed in the culture supernatant of transfected 293T cells. The purified S377-588-Fc protein efficiently binds to dipeptidyl peptidase 4 (DPP4), the receptor of MERS-CoV, and potently inhibited MERS-CoV infection, suggesting its potential to be further developed as a therapeutic modality for treating MERS-CoV infection and saving the patients' lives. The recombinant S377-588-Fc is able to induce in the vaccinated mice strong MERS-CoV S-specific antibodies, which blocks the binding of RBD to DPP4 receptor and effectively neutralizes MERS-CoV infection. These findings indicate that this truncated RBD protein shows promise for further development as an effective and safe vaccine for the prevention of MERS-CoV infection.