title: Cross-reactive influenza-specific antibody-dependent cellular cytotoxicity antibodies in the absence of neutralizing antibodies.
abstract: A better understanding of immunity to influenza virus is needed to generate cross-protective vaccines. Engagement of Ab-dependent cellular cytotoxicity (ADCC) Abs by NK cells leads to killing of virus-infected cells and secretion of antiviral cytokines and chemokines. ADCC Abs may target more conserved influenza virus Ags compared with neutralizing Abs. There has been minimal interest in influenza-specific ADCC in recent decades. In this study, we developed novel assays to assess the specificity and function of influenza-specific ADCC Abs. We found that healthy influenza-seropositive young adults without detectable neutralizing Abs to the hemagglutinin of the 1968 H3N2 influenza strain (A/Aichi/2/1968) almost always had ADCC Abs that triggered NK cell activation and in vitro elimination of influenza-infected human blood and respiratory epithelial cells. Furthermore, we detected ADCC in the absence of neutralization to both the recent H1N1 pandemic strain (A/California/04/2009) as well as the avian H5N1 influenza hemagglutinin (A/Anhui/01/2005). We conclude that there is a remarkable degree of cross-reactivity of influenza-specific ADCC Abs in seropositive humans. Targeting cross-reactive influenza-specific ADCC epitopes by vaccination could lead to improved influenza vaccines.
authors: Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia.
authors: Sinthujan
authors: S
authors: Jegaskanda
authors: Emma R
authors: ER
authors: Job
authors: Marit
authors: M
authors: Kramski
authors: Karen
authors: K
authors: Laurie
authors: Gamze
authors: G
authors: Isitman
authors: Robert
authors: R
authors: de Rose
authors: Wendy R
authors: WR
authors: Winnall
authors: Ivan
authors: I
authors: Stratov
authors: Andrew G
authors: AG
authors: Brooks
authors: Patrick C
authors: PC
authors: Reading
authors: Stephen J
authors: SJ
authors: Kent
mesh_terms: D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000378:metabolism*; D000918:Antibody Specificity / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D002675:Child, Preschool; D003429:Cross Reactions / Q000276:immunology; D006385:Hemagglutination Inhibition Tests / Q000379:methods; D006389:Hemagglutinins, Viral / Q000378:metabolism; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000378:metabolism; D007252:Influenza Vaccines / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D008254:Macaca nemestrina; D008875:Middle Aged; D009500:Neutralization Tests / Q000379:methods*; D011485:Protein Binding / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D006389:Hemagglutinins, Viral; D007252:Influenza Vaccines