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Plant-Produced Recombinant Influenza A Virus Candidate Vaccine Based on Flagellin Linked to Conservative Fragments of M2 Protein and Hemagglutintin

1
Institute of Bioengineering, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow 101000, Russia
2
Research Institute of Influenza, Russian Ministry of Health, St. Petersburg 23805, Russia
*
Author to whom correspondence should be addressed.
Plants 2020, 9(2), 162; https://doi.org/10.3390/plants9020162
Received: 24 October 2019 / Revised: 14 January 2020 / Accepted: 24 January 2020 / Published: 29 January 2020
(This article belongs to the Special Issue Plant Molecular Farming)
The development of recombinant influenza vaccines with broad spectrum protection is an important task. The combination of conservative viral antigens, such as M2e, the extracellular domain of the transmembrane protein M2, and conserved regions of the second subunit of hemagglutinin (HA), provides an opportunity for the development of universal influenza vaccines. Immunogenicity of the antigens could be enhanced by fusion to bacterial flagellin, the ligand for Toll-like receptor 5, acting as a powerful mucosal adjuvant. In this study, we report the transient expression in plants of a recombinant protein comprising flagellin of Salmonella typhimurium fused to the conserved region of the second subunit of HA (76–130 a.a.) of the first phylogenetic group of influenza A viruses and four tandem copies of the M2e peptide. The hybrid protein was expressed in Nicotiana benthamiana plants using the self-replicating potato virus X-based vector pEff up to 300 µg/g of fresh leaf tissue. The intranasal immunization of mice with purified fusion protein induced high levels of M2e-specific serum antibodies and provided protection against lethal challenge with influenza A virus strain A/Aichi/2/68(H3N2). Our results show that M2e and hemagglutinin-derived peptide can be used as important targets for the development of a plant-produced vaccine against influenza. View Full-Text
Keywords: influenza; plant; vaccine; flagellin; M2e peptide; hemagglutinin influenza; plant; vaccine; flagellin; M2e peptide; hemagglutinin
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Blokhina, E.A.; Mardanova, E.S.; Stepanova, L.A.; Tsybalova, L.M.; Ravin, N.V. Plant-Produced Recombinant Influenza A Virus Candidate Vaccine Based on Flagellin Linked to Conservative Fragments of M2 Protein and Hemagglutintin. Plants 2020, 9, 162.

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