title: Cross-reactive influenza-specific antibody-dependent cellular cytotoxicity in intravenous immunoglobulin as a potential therapeutic against emerging influenza viruses.
abstract: BACKGROUND
  Intravenous immunoglobulin (IVIG) is a purified pool of human antibodies from thousands of donors that is used to prevent or treat primary immune deficiency, several infectious diseases, and autoimmune diseases. The antibodies that mediate antibody-dependent cellular cytotoxicity (ADCC) against heterologous influenza strains may be present in IVIG preparations.
  
  
  METHODS
  We tested 8 IVIG preparations prior to the 2009 H1N1 swine-origin influenza pandemic and 10 IVIG preparations made after 2010 for their ability to mediate influenza-specific ADCC.
  
  
  RESULTS
  ADCC mediating antibodies to A(H1N1)pdm09 hemagglutinin (HA) and neuraminidase (NA) were detected in IVIG preparations prior to the 2009-H1N1 pandemic. The HA-specific ADCC targeted both the HA1 and HA2 regions of A(H1N1)pdm09 HA and was capable of recognizing a broad range of HA proteins including those from recent avian influenza strains A(H5N1) and A(H7N9). The low but detectable ADCC recognition of A(H7N9) was likely due to rare individuals in the population contributing cross-reactive antibodies to IVIG.
  
  
  CONCLUSIONS
  IVIG preparations contain broadly cross-reactive ADCC mediating antibodies. IVIG may provide at least some level of protection for individuals at high risk of severe influenza disease, especially during influenza pandemics prior to the development of effective vaccines.
authors.affiliation: Department of Microbiology and Immunology, at the Peter Doherty Institute for Infection and Immunity, University of Melbourne.
authors.forename: Sinthujan
authors.initials: S
authors.lastname: Jegaskanda
authors.affiliation: BioCSL Ltd, Parkville, Victoria.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Vandenberg
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, North Melbourne, Victoria, Australia.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Laurie
authors.affiliation: Department of Microbiology and Immunology, at the Peter Doherty Institute for Infection and Immunity, University of Melbourne.
authors.forename: Liyen
authors.initials: L
authors.lastname: Loh
authors.affiliation: Department of Microbiology and Immunology, at the Peter Doherty Institute for Infection and Immunity, University of Melbourne.
authors.forename: Marit
authors.initials: M
authors.lastname: Kramski
authors.affiliation: Department of Microbiology and Immunology, at the Peter Doherty Institute for Infection and Immunity, University of Melbourne.
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Winnall
authors.affiliation: Department of Microbiology and Immunology, at the Peter Doherty Institute for Infection and Immunity, University of Melbourne.
authors.forename: Katherine
authors.initials: K
authors.lastname: Kedzierska
authors.affiliation: Department of Microbiology and Immunology, at the Peter Doherty Institute for Infection and Immunity, University of Melbourne BioCSL Ltd, Parkville, Victoria.
authors.forename: Steven
authors.initials: S
authors.lastname: Rockman
authors.affiliation: Department of Microbiology and Immunology, at the Peter Doherty Institute for Infection and Immunity, University of Melbourne.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology*; D005260:Female; D006386:Hemagglutination Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D064766:Influenza A Virus, H7N9 Subtype / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology* / Q000628:therapy*; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D016756:Immunoglobulins, Intravenous
keywords: ADCC; IVIG; NK cells; influenza; swine-origin influenza virus