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Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity
Published on: June 25, 2015
[Immunogenicity of recombinant proteins including ectodomain of M2 influenza virus A]
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.
Insights
Developing effective influenza vaccines is crucial. This study shows flagellin-M2e fusion proteins enhance immunogenicity against human and avian influenza strains.
Area of Science:
- * Virology and immunology research.
- * Development of novel vaccine candidates.
- * Molecular biology and protein engineering.
Context:
- * Influenza viruses pose a significant global health threat.
- * The M2e protein is a conserved target for universal influenza vaccines.
- * Current vaccine strategies require continuous improvement.
Purpose:
- * To develop and compare two recombinant M2e-based vaccine candidates.
- * To evaluate the immunogenicity and efficacy of these candidates.
- * To assess the potential for broad protection against influenza A viruses.
Summary:
- * Two recombinant proteins were engineered: flagellin fused to M2e, and M2e peptides non-covalently linked to hepatitis B core antigen (HBc).
- * Covalent flagellin-M2e fusion significantly enhanced immunogenicity compared to HBc-M2e.
- * Flagellin-M2e induced a strong IgG1 response, while HBc-M2e promoted a balanced Th1/Th2 response.
- * Immunized mice showed reduced viral titers after lethal influenza A challenge.
- * Both vaccine candidates demonstrated potential for cross-protection against human and avian influenza strains.
Impact:
- * Demonstrates the superior immunogenicity of flagellin as a carrier for M2e.
- * Highlights the potential of M2e-based vaccines for broad influenza A virus protection.
- * Provides a foundation for developing universal influenza vaccines targeting both human and avian strains.
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