A Recombinant Influenza A/H1N1 Carrying A Short Immunogenic Peptide of MERS-CoV as Bivalent Vaccine in BALB/c Mice.

Mahmoud Shehata,Sara Mahmoud,Rabeh El-Shesheny,Richard Webby,Ahmed Mostafa,Ghazi Kayali,Ahmed Kandeil,Mokhtar Gomaa,Mohamed A Ali

doi:10.3390/pathogens8040281

Abstract

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) became a global human health threat since its first documentation in humans in 2012. An efficient vaccine for the prophylaxis of humans in hotspots of the infection (e.g., Saudi Arabia) is necessary but no commercial vaccines are yet approved. In this study, a chimeric DNA construct was designed to encode an influenza A/H1N1 NA protein which is flanking immunogenic amino acids (aa) 736–761 of MERS-CoV spike protein. Using the generated chimeric construct, a novel recombinant vaccine strain against pandemic influenza A virus (H1N1pdm09) and MERS-CoV was generated (chimeric bivalent 5 + 3). The chimeric bivalent 5 + 3 vaccine strain comprises a recombinant PR8-based vaccine, expressing the PB1, HA, and chimeric NA of pandemic 2009 H1N1. Interestingly, an increase in replication efficiency of the generated vaccine strain was observed when compared to the PR8-based 5 + 3 H1N1pdm09 vaccine strain that lacks the MERS-CoV spike peptide insert. In BALB/c mice, the inactivated chimeric bivalent vaccine induced potent and specific neutralizing antibodies against MERS-CoV and H1N1pdm09. This novel approach succeeded in developing a recombinant influenza virus with potential use as a bivalent vaccine against H1N1pdm09 and MERS-CoV. This approach provides a basis for the future development of chimeric influenza-based vaccines against MERS-CoV and other viruses.

Highlights

A novel human coronavirus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), was first detected in September 2012 in Saudi Arabia in a patient showing fever, shortness of breath, cough, and expectoration [1]
Using self-limited viruses as vectors for the immunogenic proteins of MERS-CoV has been applied in many studies
The rescued bivalent and control viruses were propagated in SPF embryonated chicken eggs for three passages and were safe to embryos at 48 h post infection

Summary

Introduction

A novel human coronavirus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), was first detected in September 2012 in Saudi Arabia in a patient showing fever, shortness of breath, cough, and expectoration [1]. Using self-limited viruses as vectors for the immunogenic proteins of MERS-CoV has been applied in many studies. One study has engineered a recombinant human adenoviral vector to encoding the full S protein or the S1 domain protein of HCoV-EMC/2012 isolate. Both adeno-based vaccines were evaluated in BALB/c mice and found to induce T-cell responses and neutralizing antibodies (nAbs) against MERS-CoV [3,4,5]. A recombinant modified vaccinia virus expressing the full S protein was developed.

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Conclusion