title: Generation and Protective Ability of Influenza Virus-Specific Antibody-Dependent Cellular Cytotoxicity in Humans Elicited by Vaccination, Natural Infection, and Experimental Challenge.
abstract: Nonneutralizing antibodies (Abs) involved in antibody-dependent cellular cytotoxicity (ADCC) may provide some protection from influenza virus infection. The ability of influenza vaccines to induce ADCC-mediating Abs (ADCC-Abs) in adults and children is unclear.
  
  
  
  We quantified ADCC-Abs in serum samples from adults who received a dose of inactivated subunit vaccine (ISV) targeting monovalent 2009 pandemic influenza A(H1N1) virus or live-attenuated influenza vaccine (LAIV) or who had laboratory-confirmed influenza A(H1N1) virus infection. We also measured ADCC-Abs in children who either received a dose of trivalent seasonal ISV followed by trivalent seasonal LAIV or 2 doses of LAIV. Finally, we assessed the ability of low and high ADCC-Ab titers to protect adults from experimental challenge with influenza A/Wisconsin/67/131/2005(H3N2) virus.
  
  
  
  Adults and children who received a dose of ISV had a robust increase in ADCC-Ab titers to both recombinant hemagglutinin (rHA) protein and homologous virus-infected cells. There was no detectable increase in titers of ADCC-Abs to rHA or virus-infected cells in adults and children who received LAIV. Higher titers (≥320) of preexisting ADCC-Abs were associated with lower virus replication and a significant reduction in total symptom scores in experimentally infected adults.
  
  
  
  ADCC-Ab titers increased following experimental influenza virus infection in adults and after ISV administration in both children and adults.
authors.affiliation: Laboratory of Infectious Diseases Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
authors.forename: Sinthujan
authors.initials: S
authors.lastname: Jegaskanda
authors.affiliation: Laboratory of Infectious Diseases.
authors.forename: Catherine
authors.initials: C
authors.lastname: Luke
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Heather D
authors.initials: HD
authors.lastname: Hickman
authors.affiliation: Department of Medicine, University of Rochester Medical Center, New York.
authors.forename: Mark Y
authors.initials: MY
authors.lastname: Sangster
authors.affiliation: Department of Pediatrics, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
authors.forename: Wendy F
authors.initials: WF
authors.lastname: Wieland-Alter
authors.affiliation: Biomarker Development.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: McBride
authors.affiliation: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jon W
authors.initials: JW
authors.lastname: Yewdell
authors.affiliation: Department of Pediatrics, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Wright
authors.affiliation: Department of Medicine, University of Rochester Medical Center, New York.
authors.forename: John
authors.initials: J
authors.lastname: Treanor
authors.affiliation: Biomarker Discovery, Genentech, South San Francisco, California.
authors.forename: Carrie M
authors.initials: CM
authors.lastname: Rosenberger
authors.affiliation: Laboratory of Infectious Diseases.
authors.forename: Kanta
authors.initials: K
authors.lastname: Subbarao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines
keywords: ADCC; immunity; influenza; vaccine