title: The impact of vaccination on the breadth and magnitude of the antibody response to influenza A viruses in HIV-infected individuals.
abstract: OBJECTIVE
  HIV-positive individuals have lower antibody titers to influenza viruses than HIV-negative individuals, and the benefits of the annual vaccinations are controversially discussed. Also, there is no information about the breadth of the antibody response in HIV-infected individuals.
  
  
  METHODS
  The binding and neutralizing antibody titers to various human and nonhuman influenza A virus strain were determined in sera from 146 HIV-infected volunteers: They were compared with those found in 305 randomly selected HIV-negative donors, and put in relation to HIV-specific parameters. Univariable and multivariable regression was used to identify HIV-specific parameters associated with the measured binding and neutralizing activity.
  
  
  METHODS
  Enzyme-linked immunosorbent assays and in-vitro neutralization assays were used to determine the binding and neutralizing antibodiy titers to homo and heterosubtypic influenza A subtypes.
  
  
  RESULTS
  We found that both homo and heterosubtypic antibody titers are lower in HIV-positive individuals. Vaccination promoted higher binding and neutralizing antibody titers to human but not to nonhuman isolates. HIV-induced immune damage (high viral load, low CD4 T-cell counts, and long untreated disease progression) is associated with impaired homosubtypic responses, but can have beneficial effects on the development of heterosubtypic antibodies, and an improved ratio of binding to neutralizing antibody titers to homosubtypic isolates.
  
  
  CONCLUSIONS
  Our results indicate that repetitive vaccinations in HIV-positive individuals enhance antibody titers to human isolates. Interestingly, development of antibody titers to conserved heterosubtypic epitopes paradoxically appeared to profit from HIV-induced immune damage, as did the ratio of binding to neutralizing antibodies.
authors.affiliation: aInstitute of Medical Virology, University of Zurich, Zurich, Switzerland bDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich cPhD Program in Microbiology and Immunology, Life Science Zurich Graduate School, Zurich, Switzerland.
authors.forename: Ines
authors.initials: I
authors.lastname: Kohler
authors.forename: Roger
authors.initials: R
authors.lastname: Kouyos
authors.forename: Matteo
authors.initials: M
authors.lastname: Bianchi
authors.forename: Christina
authors.initials: C
authors.lastname: Grube
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Wyrzucki
authors.forename: Huldrych F
authors.initials: HF
authors.lastname: Günthard
authors.forename: Lars
authors.initials: L
authors.lastname: Hangartner
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood*; D000917:Antibody Formation; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology*; D006801:Humans; D064789:Immunity, Heterologous; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007252:Influenza Vaccines