title: Prevalence and predictors for homo- and heterosubtypic antibodies against influenza a virus.
abstract: BACKGROUND
  The effectiveness of trivalent influenza vaccination has been confirmed in several studies. To date, it is not known whether repeated exposure and vaccination to influenza promote production of cross-reactive antibodies. Furthermore, how strains encountered earlier in life imprint the immune response is currently poorly understood.
  
  
  METHODS
  To determine the prevalence for human homo- and heterosubtypic antibody responses, we scrutinized serum samples from 305 healthy volunteers for hemagglutinin-binding and -neutralizing antibodies against several strains and subtypes of influenza A. Statistical analyses were then performed to establish the association of measured values with potential predictors.
  
  
  RESULTS
  It was found that vaccination not only promoted higher binding and neutralizing antibody titers to homosubtypic influenza isolates but also increased heterosubtypic human immune responses. Both binding and neutralizing antibody titers in relation with age of the donors mirrored the course of the different influenza strain circulation during the last century. Advanced age appeared to be of advantage for both binding and neutralizing titers to most subtypes. In contrast, the first virus subtype encountered was found to imprint to some degree subsequent antibody responses. Antibodies to recent strains, however, primarily seemed to be promoted by vaccination.
  
  
  CONCLUSIONS
  We provide evidence that vaccinations stimulate both homo- and heterosubtypic immune responses in young and middle-aged as well as more senior individuals. Our analyses suggest that influenza vaccinations not only prevent infection against currently circulating strains but can also stimulate broader humoral immune responses that potentially attenuate infections with zoonotic or antigenically shifted strains.
authors.affiliation: Institute of Medical Virology, University of Zurich Microbiology and Immunology, Life Science Zurich Graduate School.
authors.forename: Ines
authors.initials: I
authors.lastname: Kohler
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland.
authors.forename: Alexandra U
authors.initials: AU
authors.lastname: Scherrer
authors.affiliation: Institute of Medical Virology, University of Zurich.
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Zagordi
authors.affiliation: Institute of Medical Virology, University of Zurich.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bianchi
authors.affiliation: Institute of Medical Virology, University of Zurich Microbiology and Immunology, Life Science Zurich Graduate School.
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Wyrzucki
authors.affiliation: Institute of Medical Virology, University of Zurich.
authors.forename: Marco
authors.initials: M
authors.lastname: Steck
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland.
authors.forename: Bruno
authors.initials: B
authors.lastname: Ledergerber
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland.
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.affiliation: Institute of Medical Virology, University of Zurich.
authors.forename: Lars
authors.initials: L
authors.lastname: Hangartner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D005260:Female; D006801:Humans; D009980:Influenza A virus / Q000145:classification / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology; D007251:Influenza, Human / Q000453:epidemiology* / Q000276:immunology* / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D012307:Risk Factors; D016036:Seroepidemiologic Studies
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007252:Influenza Vaccines
keywords: heterosubtypic antibodies; influenza virus; predictors; prevalence