Abstract
Two recombinant proteins with three copies of the ectodomain of the conserved influenza protein M2 (M2e) of influenza viruses were developed: A (H1N1)pdm09, A/Kurgan/05/05 (H5N1), and M2e consensus sequence of the human influenza A virus (H1N1, H2N2, H3N2) based on flagellin and core antigen of hepatitis B (HBc). The first recombinant protein comprised flagellin fused to three tandem copies of M2e, the second preparation was based on non-covalent interaction between M2e peptides and HBc. The immunogenicity of two preparations was comparatively tested. A covalent linkage of flagellin with M2e significant increased the immunogenicity of the target antigen compared with non-covalent interaction M2e and HBc. Flagellin as a protein carrier of M2e induced mainly IgG1 subclass, whereas HBc stimulated more balanced Th1/Th2 response. Our study showed a decrease in the viral titers in lung tissues of immunized mice after lethal challenge of A/PR/8/34 (H1N1). The study revealed a possibility to obtain a vaccine preparation with equal immunogenicity both against human influenza viruses and highly pathogenic avian influenza viruses.
Publication types
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English Abstract
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Antibodies, Viral / blood
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Antibodies, Viral / immunology*
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Cross Protection
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Flagellin / genetics*
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Flagellin / immunology
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Gene Expression
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Humans
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Immunoglobulin G / blood
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Immunoglobulin G / immunology
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Influenza A Virus, H1N1 Subtype / genetics
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Influenza A Virus, H1N1 Subtype / immunology
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Influenza A Virus, H2N2 Subtype / genetics
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Influenza A Virus, H2N2 Subtype / immunology
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Influenza A Virus, H3N2 Subtype / genetics
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Influenza A Virus, H3N2 Subtype / immunology
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Influenza A Virus, H5N1 Subtype / genetics
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Influenza A Virus, H5N1 Subtype / immunology
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Influenza Vaccines / administration & dosage
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Influenza Vaccines / genetics
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Influenza Vaccines / immunology*
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Influenza, Human / immunology
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Influenza, Human / prevention & control*
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Influenza, Human / virology
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Mice
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Molecular Sequence Data
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Orthomyxoviridae Infections / immunology
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Orthomyxoviridae Infections / prevention & control*
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Orthomyxoviridae Infections / virology
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Protein Structure, Tertiary
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Recombinant Fusion Proteins / administration & dosage
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology*
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Vaccination
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Vaccines, Synthetic
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Viral Load
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Viral Matrix Proteins / genetics*
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Viral Matrix Proteins / immunology
Substances
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Antibodies, Viral
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Immunoglobulin G
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Influenza Vaccines
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M2 protein, Influenza A virus
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Recombinant Fusion Proteins
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Vaccines, Synthetic
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Viral Matrix Proteins
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Flagellin