Highly Immunogenic Nanoparticles Based on a Fusion Protein Comprising the M2e of Influenza A Virus and a Lipopeptide
The highly conserved extracellular domain of the transmembrane protein M2 (M2e) of the influenza A virus is a promising target for the development of broad-spectrum vaccines. However, M2e is a poor immunogen by itself and must be linked to an appropriate carrier to induce an efficient immune respons...
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doaj-319e9e74bcc0464f8505d437e06158bc2020-11-25T03:55:49ZengMDPI AGViruses1999-49152020-10-01121133113310.3390/v12101133Highly Immunogenic Nanoparticles Based on a Fusion Protein Comprising the M2e of Influenza A Virus and a LipopeptideAnna A. Zykova0Elena A. Blokhina1Roman Y. Kotlyarov2Liudmila A. Stepanova3Liudmila M. Tsybalova4Victor V. Kuprianov5Nikolai V. Ravin6Institute of Bioengineering, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow 119071, RussiaInstitute of Bioengineering, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow 119071, RussiaInstitute of Bioengineering, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow 119071, 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 119071, RussiaInstitute of Bioengineering, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow 119071, RussiaThe highly conserved extracellular domain of the transmembrane protein M2 (M2e) of the influenza A virus is a promising target for the development of broad-spectrum vaccines. However, M2e is a poor immunogen by itself and must be linked to an appropriate carrier to induce an efficient immune response. In this study, we obtained recombinant mosaic proteins containing tandem copies of M2e fused to a lipopeptide from <i>Neisseria meningitidis</i> surface lipoprotein Ag473 and alpha-helical linkers and analyzed their immunogenicity. Six fusion proteins, comprising four or eight tandem copies of M2e flanked by alpha-helical linkers, lipopeptides, or a combination of both of these elements, were produced in <i>Escherichia coli</i>. The proteins, containing both alpha-helical linkers and lipopeptides at each side of M2e repeats, formed nanosized particles, but no particulate structures were observed in the absence of lipopeptides. Animal study results showed that proteins with lipopeptides induced strong M2e-specific antibody responses in the absence of external adjuvants compared to similar proteins without lipopeptides. Thus, the recombinant M2e-based proteins containing alpha-helical linkers and <i>N. meningitidis</i> lipopeptide sequences at the N- and C-termini of four or eight tandem copies of M2e peptide are promising vaccine candidates.https://www.mdpi.com/1999-4915/12/10/1133influenzarecombinant vaccineM2e peptidelipopeptidenanoparticle |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anna A. Zykova Elena A. Blokhina Roman Y. Kotlyarov Liudmila A. Stepanova Liudmila M. Tsybalova Victor V. Kuprianov Nikolai V. Ravin |
spellingShingle |
Anna A. Zykova Elena A. Blokhina Roman Y. Kotlyarov Liudmila A. Stepanova Liudmila M. Tsybalova Victor V. Kuprianov Nikolai V. Ravin Highly Immunogenic Nanoparticles Based on a Fusion Protein Comprising the M2e of Influenza A Virus and a Lipopeptide Viruses influenza recombinant vaccine M2e peptide lipopeptide nanoparticle |
author_facet |
Anna A. Zykova Elena A. Blokhina Roman Y. Kotlyarov Liudmila A. Stepanova Liudmila M. Tsybalova Victor V. Kuprianov Nikolai V. Ravin |
author_sort |
Anna A. Zykova |
title |
Highly Immunogenic Nanoparticles Based on a Fusion Protein Comprising the M2e of Influenza A Virus and a Lipopeptide |
title_short |
Highly Immunogenic Nanoparticles Based on a Fusion Protein Comprising the M2e of Influenza A Virus and a Lipopeptide |
title_full |
Highly Immunogenic Nanoparticles Based on a Fusion Protein Comprising the M2e of Influenza A Virus and a Lipopeptide |
title_fullStr |
Highly Immunogenic Nanoparticles Based on a Fusion Protein Comprising the M2e of Influenza A Virus and a Lipopeptide |
title_full_unstemmed |
Highly Immunogenic Nanoparticles Based on a Fusion Protein Comprising the M2e of Influenza A Virus and a Lipopeptide |
title_sort |
highly immunogenic nanoparticles based on a fusion protein comprising the m2e of influenza a virus and a lipopeptide |
publisher |
MDPI AG |
series |
Viruses |
issn |
1999-4915 |
publishDate |
2020-10-01 |
description |
The highly conserved extracellular domain of the transmembrane protein M2 (M2e) of the influenza A virus is a promising target for the development of broad-spectrum vaccines. However, M2e is a poor immunogen by itself and must be linked to an appropriate carrier to induce an efficient immune response. In this study, we obtained recombinant mosaic proteins containing tandem copies of M2e fused to a lipopeptide from <i>Neisseria meningitidis</i> surface lipoprotein Ag473 and alpha-helical linkers and analyzed their immunogenicity. Six fusion proteins, comprising four or eight tandem copies of M2e flanked by alpha-helical linkers, lipopeptides, or a combination of both of these elements, were produced in <i>Escherichia coli</i>. The proteins, containing both alpha-helical linkers and lipopeptides at each side of M2e repeats, formed nanosized particles, but no particulate structures were observed in the absence of lipopeptides. Animal study results showed that proteins with lipopeptides induced strong M2e-specific antibody responses in the absence of external adjuvants compared to similar proteins without lipopeptides. Thus, the recombinant M2e-based proteins containing alpha-helical linkers and <i>N. meningitidis</i> lipopeptide sequences at the N- and C-termini of four or eight tandem copies of M2e peptide are promising vaccine candidates. |
topic |
influenza recombinant vaccine M2e peptide lipopeptide nanoparticle |
url |
https://www.mdpi.com/1999-4915/12/10/1133 |
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