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

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Pathogens. 2019 Dec 2;8(4). pii: E281. doi: 10.3390/pathogens8040281. A Recombinant Influenza A/H1N1 Carrying A Short Immunogenic Peptide of MERS-CoV as Bivalent Vaccine in BALB/c Mice.

Shehata MM¹, Kandeil A¹, Mostafa A¹, Mahmoud SH¹, Gomaa MR¹, El-Shesheny R^1,2, Webby R², Kayali G^3,4, Ali MA¹.
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1 Center of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Cairo 12622, Egypt. 2 Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. 3 Department of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas, Houston, TX 77030, USA. 4 Human Link, Baabda 1109, Lebanon.

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.


KEYWORDS:

H1N1pdm; MERS-CoV; influenza vaccine; reverse genetics

PMID: 31810359 DOI: 10.3390/pathogens8040281
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