CD8+ T Cells Responding to the Middle East Respiratory Syndrome Coronavirus Nucleocapsid Protein Delivered by Vaccinia Virus MVA in Mice

Viruses. 2018 Dec 16;10(12):718. doi: 10.3390/v10120718.

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV), a novel infectious agent causing severe respiratory disease and death in humans, was first described in 2012. Antibodies directed against the MERS-CoV spike (S) protein are thought to play a major role in controlling MERS-CoV infection and in mediating vaccine-induced protective immunity. In contrast, relatively little is known about the role of T cell responses and the antigenic targets of MERS-CoV that are recognized by CD8+ T cells. In this study, the highly conserved MERS-CoV nucleocapsid (N) protein served as a target immunogen to elicit MERS-CoV-specific cellular immune responses. Modified Vaccinia virus Ankara (MVA), a safety-tested strain of vaccinia virus for preclinical and clinical vaccine research, was used for generating MVA-MERS-N expressing recombinant N protein. Overlapping peptides spanning the whole MERS-CoV N polypeptide were used to identify major histocompatibility complex class I/II-restricted T cell responses in BALB/c mice immunized with MVA-MERS-N. We have identified a H2-d restricted decamer peptide epitope in the MERS-N protein with CD8+ T cell antigenicity. The identification of this epitope, and the availability of the MVA-MERS-N candidate vaccine, will help to evaluate MERS-N-specific immune responses and the potential immune correlates of vaccine-mediated protection in the appropriate murine models of MERS-CoV infection.

Keywords: MERS-CoV; MERS-CoV nucleocapsid protein; MVA vaccine; murine CD8+ T cell epitope.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Coronavirus Infections / immunology*
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Immunity, Cellular
  • Mice
  • Mice, Inbred BALB C
  • Middle East Respiratory Syndrome Coronavirus / immunology*
  • Nucleocapsid Proteins / genetics
  • Nucleocapsid Proteins / immunology*
  • Recombinant Proteins / immunology
  • Vaccination
  • Vaccinia virus / genetics
  • Vaccinia virus / immunology
  • Viral Vaccines / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes, T-Lymphocyte
  • Nucleocapsid Proteins
  • Recombinant Proteins
  • Viral Vaccines