title: Influenza-Specific Antibody-Dependent Phagocytosis.
abstract: Immunity to human influenza A virus (IAV) infection is only partially understood. Broadly non-neutralizing antibodies may assist in reducing disease but have not been well characterized.
  
  
  
  We measured internalization of opsonized, influenza protein-coated fluorescent beads and live IAV into a monocytic cell line to study antibody-dependent phagocytosis (ADP) against multiple influenza hemagglutinin (HA) subtypes. We analyzed influenza HA-specific ADP in healthy human donors, in preparations of intravenous immunoglobulin (IVIG), and following IAV infection of humans and macaques.
  
  
  
  We found that both sera from healthy adults and IVIG preparations had broad ADP to multiple seasonal HA proteins and weak cross-reactive ADP to non-circulating HA proteins. The ADP in experimentally influenza-infected macaque plasma and naturally influenza-infected human sera mediated phagocytosis of both homologous and heterologous IAVs. Further, the IAV phagocytosed in an antibody-mediated manner had reduced infectivity in vitro.
  
  
  
  We conclude that IAV infections in humans and macaques leads to the development of influenza-specific ADP that can clear IAV infection in vitro. Repeated exposure of humans to multiple IAV infections likely leads to the development of ADP that is cross-reactive to strains not previously encountered. Further analyses of the protective capacity of broadly reactive influenza-specific ADP is warranted.
authors.affiliation: Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Ana-Sosa-Batiz
authors.affiliation: Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.
authors.forename: Hillary
authors.initials: H
authors.lastname: Vanderven
authors.affiliation: Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.
authors.forename: Sinthujan
authors.initials: S
authors.lastname: Jegaskanda
authors.affiliation: Drug Delivery, Disposition and Dynamics laboratory, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash University, Parkville, Australia.
authors.forename: Angus
authors.initials: A
authors.lastname: Johnston
authors.affiliation: Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.|bioCSL Ltd, Parkville, Victoria, Australia.
authors.forename: Steven
authors.initials: S
authors.lastname: Rockman
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
authors.forename: Karen
authors.initials: K
authors.lastname: Laurie
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Barr
authors.affiliation: Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.|WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
authors.forename: Patrick
authors.initials: P
authors.lastname: Reading
authors.affiliation: Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.
authors.forename: Marit
authors.initials: M
authors.lastname: Lichtfuss
authors.affiliation: Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.|Melbourne Sexual Health Centre, Central Clinical School, Monash University, Melbourne, Australia.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Parkville, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis* / Q000494:pharmacology; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000494:pharmacology; D002460:Cell Line; D056738:Cross Protection; D003429:Cross Reactions; D005456:Fluorescent Dyes / Q000737:chemistry; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000276:immunology; D006801:Humans; D055767:Immobilized Proteins / Q000737:chemistry / Q000276:immunology; D007106:Immune Sera / Q000737:chemistry / Q000494:pharmacology; D056724:Immunity, Humoral; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D008254:Macaca nemestrina; D008863:Microspheres; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology; D010587:Phagocytosis / Q000187:drug effects*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D005456:Fluorescent Dyes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D055767:Immobilized Proteins; D007106:Immune Sera; D016756:Immunoglobulins, Intravenous