title: 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.
abstract: 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.
authors: Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America.
authors: Lanying
authors: L
authors: Du
authors: Zhihua
authors: Z
authors: Kou
authors: Cuiqing
authors: C
authors: Ma
authors: Xinrong
authors: X
authors: Tao
authors: Lili
authors: L
authors: Wang
authors: Guangyu
authors: G
authors: Zhao
authors: Yaoqing
authors: Y
authors: Chen
authors: Fei
authors: F
authors: Yu
authors: Chien-Te K
authors: CT
authors: Tseng
authors: Yusen
authors: Y
authors: Zhou
authors: Shibo
authors: S
authors: Jiang
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D017934:Coronavirus / Q000502:physiology*; D018360:Crystallography, X-Ray; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007074:Immunoglobulin G / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D017434:Protein Structure, Tertiary; D011961:Receptors, Fc / Q000378:metabolism*; D011994:Recombinant Proteins / Q000276:immunology; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D064370:Spike Glycoprotein, Coronavirus / Q000378:metabolism*; D014611:Vaccination; D014612:Vaccines / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology* / Q000627:therapeutic use
chemical_list: D057134:Antibodies, Neutralizing; D007106:Immune Sera; D007074:Immunoglobulin G; D011961:Receptors, Fc; D011994:Recombinant Proteins; D064370:Spike Glycoprotein, Coronavirus; D014612:Vaccines; D014765:Viral Vaccines