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Author Spotlight: Investigating Bacteriophage-Induced Immune Responses in Gnotobiotic Mice
Published on: January 26, 2024
Protection against Influenza A Virus Challenge with M2e-Displaying Filamentous Escherichia coli Phages
Lei Deng1, Lorena Itatí Ibañez1, Veronique Van den Bossche1
1Medical Biotechnology Center, VIB, Technologiepark 927, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, Ghent, Belgium.
Abstract:
Human influenza viruses are responsible for annual epidemics and occasional pandemics that cause severe illness and mortality in all age groups worldwide. Matrix protein 2 (M2) of influenza A virus is a tetrameric type III membrane protein that functions as a proton-selective channel. The extracellular domain of M2 (M2e) is conserved in human and avian influenza A viruses and is being pursued as a component for a universal influenza A vaccine. To develop a M2e vaccine that is economical and easy to purify, we genetically fused M2e amino acids 2-16 to the N-terminus of pVIII, the major coat protein of filamentous bacteriophage f88. We show that the resulting recombinant f88-M2e2-16 phages are replication competent and display the introduced part of M2e on the phage surface. Immunization of mice with purified f88-M2e2-16 phages in the presence of incomplete Freund's adjuvant, induced robust M2e-specific serum IgG and protected BALB/c mice against challenge with human and avian influenza A viruses. Thus, replication competent filamentous bacteriophages can be used as efficient and economical carriers to display conserved B cell epitopes of influenza A.
Insights
Researchers developed a novel universal influenza A vaccine using bacteriophage carriers displaying a conserved M2e epitope. This economical approach successfully immunized mice, offering protection against both human and avian influenza A virus strains.
Area of Science:
- Virology
- Immunology
- Biotechnology
Background:
- Influenza A viruses cause global epidemics and pandemics, necessitating effective vaccines.
- The extracellular domain of Matrix protein 2 (M2e) is a conserved target for a universal influenza A vaccine.
- Current vaccine development faces challenges in cost and purification.
Purpose of the Study:
- To create an economical and easily purified M2e-based universal influenza A vaccine.
- To utilize filamentous bacteriophages as carriers for displaying M2e epitopes.
Main Methods:
- Genetically fused M2e (amino acids 2-16) to the N-terminus of bacteriophage f88's pVIII coat protein.
- Produced replication-competent recombinant f88-M2e2-16 phages displaying M2e on their surface.
- Immunized BALB/c mice with purified f88-M2e2-16 phages and incomplete Freund's adjuvant.
Main Results:
- Recombinant f88-M2e2-16 phages were replication competent and successfully displayed the M2e epitope.
- Immunization induced robust M2e-specific serum IgG responses in mice.
- Vaccinated mice were protected against challenge with both human and avian influenza A viruses.
Conclusions:
- Replication-competent filamentous bacteriophages are effective and economical carriers for displaying conserved influenza A B cell epitopes.
- This phage-based platform shows promise for developing a universal influenza A vaccine.
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