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

Svenja Veit,Sylvia Jany,Robert Fux,Asisa Volz,Gerd Sutter

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.

Highlights

The Middle East respiratory syndrome coronavirus (MERS-CoV), a hitherto unknown β-coronavirus, emerged as a causative agent of a severe respiratory disease in humans in 2012
Recombinant virus Modified Vaccinia virus Ankara (MVA)-MERS-N was formed in chicken embryo fibroblasts (CEF) that were infected with MVA and transfected with the MVA vector plasmid pIIIH5red-MERS-N (Figure 1a)
The development of these tools is hampered by the fact that we still know little about the relevant viral antigens and the overall pathogenesis of the MERS-CoV infection

Summary

Introduction

The Middle East respiratory syndrome coronavirus (MERS-CoV), a hitherto unknown β-coronavirus, emerged as a causative agent of a severe respiratory disease in humans in 2012. This new coronavirus was first isolated from the sputum of a patient suffering from severe pneumonia and renal failure [1]. Saudi Arabia, which accounts for the majority of primary community-acquired cases. Many of those primary cases are due to virus exposure through direct contact with dromedary camels, the primary animal reservoir of MERS-CoV. Most of the MERS-CoV infections occur within the Arabian Peninsula, i.e., Saudi Arabia, Qatar, and United Arab

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Conclusion