title: Influenza virus-specific antibody dependent cellular cytoxicity induced by vaccination or natural infection.
abstract: Influenza viruses are responsible for substantial morbidity and mortality during seasonal epidemics. Vaccination is the most effective method to prevent infection, however due to antigenic drift of the viral surface protein hemagglutinin (HA), annual influenza virus vaccination is required. In addition to seasonal viruses, certain (avian) influenza A viruses of other subtypes, like H5N1 or H7N9, cause sporadic zoonotic infections. Therefore, the availability of game-changing novel vaccines that induce "universal" immune responses to a wide variety of influenza A virus subtypes is highly desirable. The quest for universal influenza vaccines has fueled the interest in broadly-reactive antibodies specific for the stalk of hemagglutinin (HA) and biological activities of antibodies other than direct virus neutralization, like antibody-dependent cellular cytotoxicity (ADCC). In the present study, we investigated the ADCC response upon influenza virus vaccination and infection in humans using a robust ADCC assay that is based on the use of recombinant HA and a continuous NK cell line that expresses FcγRIII (CD16). This assay offers advantages over existing methods, like ease to perform and possibilities to standardize. We showed that HA-specific ADCC mediating antibodies are induced by vaccination with adjuvanted trivalent seasonal and monovalent H1N1pdm09 inactivated vaccines, and by infection with H1N1pdm09 virus. In addition, the use of chimeric influenza HA with a H1 stem but antigenically irrelevant head domain derived from an avian virus allowed detection of H1-stalk-specific ADCC mediating antibodies. This assay will facilitate the assessment of ADCC mediating serum antibodies after (universal) influenza vaccination or infection and may define ADCC activity as a correlate of (cross-) protection in the future.
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Rory D
authors.initials: RD
authors.lastname: de Vries
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Nella J
authors.initials: NJ
authors.lastname: Nieuwkoop
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Mark
authors.initials: M
authors.lastname: Pronk
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Erwin
authors.initials: E
authors.lastname: de Bruin
authors.affiliation: Center for Vaccinology, Ghent University and Ghent University Hospital, Ghent, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
authors.affiliation: Department of Medical Microbiology, Albert Schweitzer Hospital, Dordrecht, The Netherlands.
authors.forename: Elisabeth G W
authors.initials: EGW
authors.lastname: Huijskens
authors.affiliation: Centers for Infectious Disease Control (Cib), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Rob S
authors.initials: RS
authors.lastname: van Binnendijk
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Florian
authors.initials: F
authors.lastname: Krammer
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Marion P G
authors.initials: MPG
authors.lastname: Koopmans
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands. Electronic address: g.rimmelzwaan@erasmusmc.nl.
authors.forename: Guus F
authors.initials: GF
authors.lastname: Rimmelzwaan
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity; D002460:Cell Line; D002648:Child; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D009975:Orthomyxoviridae / Q000276:immunology*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines
keywords: Antibodies; Antibody dependent cellular cytotoxicity; Influenza virus; Natural killer cells