title: Antibody-dependent cellular cytotoxicity is associated with control of pandemic H1N1 influenza virus infection of macaques.
abstract: Emerging influenza viruses pose a serious risk to global human health. Recent studies in ferrets, macaques, and humans suggest that seasonal H1N1 (sH1N1) infection provides some cross-protection against 2009 pandemic influenza viruses (H1N1pdm), but the correlates of cross-protection are poorly understood. Here we show that seasonal infection of influenza-naïve Indian rhesus macaques (Macaca mulatta) with A/Kawasaki/173/2001 (sH1N1) virus induces antibodies capable of binding the hemagglutinin (HA) of both the homologous seasonal virus and the antigenically divergent A/California/04/2009 (H1N1pdm) strain in the absence of detectable H1N1pdm-specific neutralizing antibodies. These influenza virus-specific antibodies activated macaque NK cells to express both CD107a and gamma interferon (IFN-γ) in the presence of HA proteins from either sH1N1 or H1N1pdm viruses. Although influenza virus-specific antibody-dependent cellular cytotoxicity (ADCC)-mediated NK cell activation diminished in titer over time following sH1N1 infection, these cells expanded rapidly within 7 days following H1N1pdm exposure. Furthermore, we found that influenza virus-specific ADCC was present in bronchoalveolar lavage fluid and was able to activate lung NK cells. We concluded that infection with a seasonal influenza virus can induce antibodies that mediate ADCC capable of recognizing divergent influenza virus strains. Cross-reactive ADCC may provide a mechanism for reducing the severity of divergent influenza virus infections.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Victoria, Australia.
authors.forename: Sinthujan
authors.initials: S
authors.lastname: Jegaskanda
authors.forename: Jason T
authors.initials: JT
authors.lastname: Weinfurter
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Friedrich
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D003429:Cross Reactions; D015870:Gene Expression; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology* / Q000378:metabolism; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000096:biosynthesis; D008253:Macaca mulatta; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D018419:Primate Diseases / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D052118:Lysosomal-Associated Membrane Protein 1; D007371:Interferon-gamma