4.5 Article

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

Journal

VACCINE
Volume 35, Issue 1, Pages 10-18

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2016.11.064

Keywords

MERS-CoV; Vaccine; Mice; NTD; RBD; Animal model

Funding

  1. National Key Research and Development Program of China [2016YFD0500301]
  2. Megaproject for Infectious Disease Research of China [2014ZX10004001-002, 2012ZX10004501-004]
  3. National Natural Sciences Fund of China [81302607, 31400787]
  4. Natural Sciences Fund of Hebei Province [H2013206108]

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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 10 mu g 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 10 mu g 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. (C) 2016 Elsevier Ltd. All rights reserved.

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