title: Universal antibodies against the highly conserved influenza fusion peptide cross-neutralize several subtypes of influenza A virus.
abstract: The fusion peptide of influenza viral hemagglutinin plays a critical role in virus entry by facilitating membrane fusion between the virus and target cells. As the fusion peptide is the only universally conserved epitope in all influenza A and B viruses, it could be an attractive target for vaccine-induced immune responses. We previously reported that antibodies targeting the first 14 amino acids of the N-terminus of the fusion peptide could bind to virtually all influenza virus strains and quantify hemagglutinins in vaccines produced in embryonated eggs. Here we demonstrate that these universal antibodies bind to the viral hemagglutinins in native conformation presented in infected mammalian cell cultures and neutralize multiple subtypes of virus by inhibiting the pH-dependant fusion of viral and cellular membranes. These results suggest that this unique, highly-conserved linear sequence in viral hemagglutinin is exposed sufficiently to be attacked by the antibodies during the course of infection and merits further investigation because of potential importance in the protection against diverse strains of influenza viruses.
authors.affiliation: Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON, Canada.
authors.forename: Anwar M
authors.initials: AM
authors.lastname: Hashem
authors.forename: Gary
authors.initials: G
authors.lastname: Van Domselaar
authors.forename: Changgui
authors.initials: C
authors.lastname: Li
authors.forename: Junzhi
authors.initials: J
authors.lastname: Wang
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: She
authors.forename: Terry D
authors.initials: TD
authors.lastname: Cyr
authors.forename: Jianhua
authors.initials: J
authors.lastname: Sui
authors.forename: Runtao
authors.initials: R
authors.lastname: He
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Marasco
authors.forename: Xuguang
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D002460:Cell Line; D004285:Dogs; D006389:Hemagglutinins, Viral / Q000276:immunology*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology / Q000502:physiology; D009980:Influenza A virus / Q000276:immunology* / Q000502:physiology; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D006389:Hemagglutinins, Viral; C458881:hemagglutinin fusogenic peptide, influenza virus