Plant-Produced Recombinant Influenza A Virus Candidate Vaccine Based on Flagellin Linked to Conservative Fragments of M2 Protein and Hemagglutintin
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...
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doaj-84a78c442a134f468f74ef231951bfa62020-11-25T01:12:28ZengMDPI AGPlants2223-77472020-01-019216210.3390/plants9020162plants9020162Plant-Produced Recombinant Influenza A Virus Candidate Vaccine Based on Flagellin Linked to Conservative Fragments of M2 Protein and HemagglutintinElena A. Blokhina0Eugenia S. Mardanova1Liudmila A. Stepanova2Liudmila M. Tsybalova3Nikolai V. Ravin4Institute of Bioengineering, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow 101000, RussiaInstitute of Bioengineering, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow 101000, RussiaResearch Institute of Influenza, Russian Ministry of Health, St. Petersburg 23805, RussiaResearch Institute of Influenza, Russian Ministry of Health, St. Petersburg 23805, RussiaInstitute of Bioengineering, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow 101000, RussiaThe 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 <i>Salmonella typhimurium</i> 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 <i>Nicotiana benthamiana</i> 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.https://www.mdpi.com/2223-7747/9/2/162influenzaplantvaccineflagellinm2e peptidehemagglutinin |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Elena A. Blokhina Eugenia S. Mardanova Liudmila A. Stepanova Liudmila M. Tsybalova Nikolai V. Ravin |
spellingShingle |
Elena A. Blokhina Eugenia S. Mardanova Liudmila A. Stepanova Liudmila M. Tsybalova Nikolai V. Ravin Plant-Produced Recombinant Influenza A Virus Candidate Vaccine Based on Flagellin Linked to Conservative Fragments of M2 Protein and Hemagglutintin Plants influenza plant vaccine flagellin m2e peptide hemagglutinin |
author_facet |
Elena A. Blokhina Eugenia S. Mardanova Liudmila A. Stepanova Liudmila M. Tsybalova Nikolai V. Ravin |
author_sort |
Elena A. Blokhina |
title |
Plant-Produced Recombinant Influenza A Virus Candidate Vaccine Based on Flagellin Linked to Conservative Fragments of M2 Protein and Hemagglutintin |
title_short |
Plant-Produced Recombinant Influenza A Virus Candidate Vaccine Based on Flagellin Linked to Conservative Fragments of M2 Protein and Hemagglutintin |
title_full |
Plant-Produced Recombinant Influenza A Virus Candidate Vaccine Based on Flagellin Linked to Conservative Fragments of M2 Protein and Hemagglutintin |
title_fullStr |
Plant-Produced Recombinant Influenza A Virus Candidate Vaccine Based on Flagellin Linked to Conservative Fragments of M2 Protein and Hemagglutintin |
title_full_unstemmed |
Plant-Produced Recombinant Influenza A Virus Candidate Vaccine Based on Flagellin Linked to Conservative Fragments of M2 Protein and Hemagglutintin |
title_sort |
plant-produced recombinant influenza a virus candidate vaccine based on flagellin linked to conservative fragments of m2 protein and hemagglutintin |
publisher |
MDPI AG |
series |
Plants |
issn |
2223-7747 |
publishDate |
2020-01-01 |
description |
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 <i>Salmonella typhimurium</i> 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 <i>Nicotiana benthamiana</i> 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. |
topic |
influenza plant vaccine flagellin m2e peptide hemagglutinin |
url |
https://www.mdpi.com/2223-7747/9/2/162 |
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