title: Protection against Influenza A Virus Challenge with M2e-Displaying Filamentous Escherichia coli Phages.
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.
authors.affiliation: Medical Biotechnology Center, VIB, Technologiepark 927, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, Ghent, Belgium.
authors.forename: Lei
authors.initials: L
authors.lastname: Deng
authors.affiliation: Medical Biotechnology Center, VIB, Technologiepark 927, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, Ghent, Belgium.
authors.forename: Lorena Itatí
authors.initials: LI
authors.lastname: Ibañez
authors.affiliation: Medical Biotechnology Center, VIB, Technologiepark 927, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, Ghent, Belgium.
authors.forename: Veronique
authors.initials: V
authors.lastname: Van den Bossche
authors.affiliation: Medical Biotechnology Center, VIB, Technologiepark 927, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, Ghent, Belgium.
authors.forename: Kenny
authors.initials: K
authors.lastname: Roose
authors.affiliation: Department of Pathobiology, Faculty of Veterinary Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Sameh A
authors.initials: SA
authors.lastname: Youssef
authors.affiliation: Department of Pathobiology, Faculty of Veterinary Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Alain
authors.initials: A
authors.lastname: de Bruin
authors.affiliation: Medical Biotechnology Center, VIB, Technologiepark 927, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, Ghent, Belgium.
authors.forename: Walter
authors.initials: W
authors.lastname: Fiers
authors.affiliation: Medical Biotechnology Center, VIB, Technologiepark 927, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 927, Ghent, Belgium.
authors.forename: Xavier
authors.initials: X
authors.lastname: Saelens
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000956:Antigens, Viral / Q000096:biosynthesis / Q000276:immunology; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics*; D003090:Coliphages / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000378:metabolism; D007252:Influenza Vaccines / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics*; D014779:Virus Replication; D000086082:Viroporin Proteins
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D011993:Recombinant Fusion Proteins; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins