The recombinant N-terminal domain of spike proteins is a potential vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV) infection

• Published in: Vaccine Vol. 35; no. 1; pp. 10 - 18
• Main Authors: Jiaming, Lan, Yanfeng, Yao, Yao, Deng, Yawei, Hu, Linlin, Bao, Baoying, Huang, Jinghua, Yan, Gao, George F., Chuan, Qin, Wenjie, Tan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 03.01.2017; Elsevier Limited
• Subjects: adjuvants; Allergy and Immunology; Aluminum; Animal model; animal models; Animals; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Antigens; blood serum; cell-mediated immunity; Coronaviridae; Coronavirus Infections - prevention & control; cytokines; Disease Models, Animal; Enzymes; Female; Health risks; humans; humoral immunity; Immune response; Immunization; Immunoassay; Immunogenicity; immunoglobulin G; Immunoglobulin G - blood; Immunoglobulins; Infections; Laboratory animals; Lung - pathology; MERS-CoV; Mice; Mice, Inbred BALB C; Middle East respiratory syndrome coronavirus; Middle East Respiratory Syndrome Coronavirus - genetics; Middle East Respiratory Syndrome Coronavirus - immunology; neutralization; neutralizing antibodies; NTD; Proteins; Public health; R&D; RBD; Research & development; Respiratory diseases; Rodents; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; staining; Studies; T-lymphocytes; T-Lymphocytes - immunology; vaccination; Vaccine; Vaccines; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology; Viral Vaccines - administration & dosage; Viral Vaccines - genetics; Viral Vaccines - immunology; Middle East; Animal model; MERS-CoV; Vaccine; Mice; RBD; NTD
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2016.11.064

The persistent public health threat of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the need for an effective MERS-CoV vaccine. Previous studies have focused mainly on the receptor-binding domain (RBD) on the spike protein of MERS-CoV. Herein, we investigated the immunogenicity and protective potential of the recombinant N-terminal domain (rNTD) of spike proteins as a vaccine candidate. BALB/c mice vaccinated with 5 or 10μg of rNTD protein demonstrated a significant humoral immune response (serum IgG and neutralizing activity). Additionally, according to the enzyme-linked immunospot, intracellular cytokine staining, and cytometric bead array assays, significant and functional T-cell immunity was induced by 10μg of the rNTD vaccination with aluminum and CpG adjuvant. Furthermore, rNTD-immunized mice showed reduced lung abnormalities in a MERS-CoV-challenge mouse model transfected with an adenoviral vector expressing human DPP4, showing protection consistent with that found with rRBD vaccination. These data show that rNTD induced potent cellular immunity and antigen-specific neutralizing antibodies in mice and that it demonstrated protective capacity against a viral challenge, indicating that rNTD is a vaccine candidate against MERS-CoV infection.