title: Induction of H7N9-Cross-Reactive Antibody-Dependent Cellular Cytotoxicity Antibodies by Human Seasonal Influenza A Viruses that are Directed Toward the Nucleoprotein.
abstract: Antibodies that mediate antibody-dependent cellular cytotoxicity (ADCC) against avian influenza virus subtypes, including H7N9 and H5N1, have been detected in human sera. Using NK cell activation and NK cytotoxicity assays, we compared ADCC-mediating antibodies (ADCC-Abs) in sera collected from healthy infants, children and adults against H7N9 virus-infected cells and recombinant hemagglutinin (HA), neuraminidase (NA), and nucleoprotein (NP) proteins. High titers of ADCC-Abs against H7N9 virus-infected cells were detected in sera from adults and children but not infants. ADCC-Abs titers directed against H7N9 HA or NA proteins. Further analysis showed that ADCC-Abs titers were significantly higher toward H7N9 NP, as compared with H7N9 HA or NA proteins, and correlated strongly with ADCC-Abs titers against H7N9 virus-infected cells. Indeed, ADCC-Abs to NPs of seasonal H1N1 and H3N2 viruses correlated strongly with ADCC-Abs to H7N9 NP, suggesting that seasonal influenza infections and vaccinations may induce these cross-reactive antibodies. Targeting ADCC-Abs to internal proteins may be a potential mechanism of universal vaccine design.
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.|Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, Victoria, Australia.
authors.forename: Sinthujan
authors.initials: S
authors.lastname: Jegaskanda
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Mary Dawn T
authors.initials: MDT
authors.lastname: Co
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Cruz
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Kanta
authors.initials: K
authors.lastname: Subbarao
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Francis A
authors.initials: FA
authors.lastname: Ennis
authors.affiliation: Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Masanori
authors.initials: M
authors.lastname: Terajima
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D002648:Child; D002675:Child, Preschool; D003429:Cross Reactions; D006388:Hemagglutinins / Q000097:blood / Q000276:immunology; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype; D053122:Influenza A Virus, H3N2 Subtype; D053124:Influenza A Virus, H5N1 Subtype; D064766:Influenza A Virus, H7N9 Subtype; D007252:Influenza Vaccines / Q000627:therapeutic use; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control; D007694:Killer Cells, Natural / Q000276:immunology; D008875:Middle Aged; D009439:Neuraminidase / Q000097:blood / Q000276:immunology; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins / Q000097:blood / Q000276:immunology*; D011994:Recombinant Proteins / Q000097:blood / Q000276:immunology; D014758:Viral Core Proteins / Q000097:blood / Q000276:immunology*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D006388:Hemagglutinins; D007252:Influenza Vaccines; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D014758:Viral Core Proteins; D009439:Neuraminidase
keywords: ADCC; antibody; antibody-dependent cellular cytotoxicity; influenza virus; nucleoprotein