1. [Immunogenicity of recombinant proteins including ectodomain of M2 influenza virus A].
- Author
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Stepanova LA, Kovaleva AA, Potapchuk MV, Korotkov AV, Kupriianov VV, Blokhina EA, Kotliarov RIu, and Tsybalova LM
- Subjects
- Amino Acid Sequence, Animals, Antibodies, Viral blood, Cross Protection, Flagellin immunology, Gene Expression, Humans, Immunoglobulin G blood, Immunoglobulin G immunology, Influenza A Virus, H1N1 Subtype genetics, Influenza A Virus, H1N1 Subtype immunology, Influenza A Virus, H2N2 Subtype genetics, Influenza A Virus, H2N2 Subtype immunology, Influenza A Virus, H3N2 Subtype genetics, Influenza A Virus, H3N2 Subtype immunology, Influenza A Virus, H5N1 Subtype genetics, Influenza A Virus, H5N1 Subtype immunology, Influenza Vaccines administration & dosage, Influenza Vaccines genetics, Influenza, Human immunology, Influenza, Human virology, Mice, Molecular Sequence Data, Orthomyxoviridae Infections immunology, Orthomyxoviridae Infections virology, Protein Structure, Tertiary, Recombinant Fusion Proteins administration & dosage, Recombinant Fusion Proteins genetics, Vaccination, Vaccines, Synthetic, Viral Load, Viral Matrix Proteins immunology, Antibodies, Viral immunology, Flagellin genetics, Influenza Vaccines immunology, Influenza, Human prevention & control, Orthomyxoviridae Infections prevention & control, Recombinant Fusion Proteins immunology, Viral Matrix Proteins genetics
- 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.
- Published
- 2013