title: Pre-vaccination immunity and immune responses to a cell culture-derived whole-virus H1N1 vaccine are similar to a seasonal influenza vaccine.
abstract: BACKGROUND
  Immune responses to novel pandemic influenza vaccines may be influenced by previous exposure to antigenically similar seasonal strains.
  
  
  METHODS
  An open-label, randomized, phase I/II study was conducted to assess the immunogenicity and safety of a non-adjuvanted, inactivated whole-virus H1N1 A/California/07/2009 vaccine. 408 subjects were stratified by age (18-59 and >60 years) and randomized 1:1 to receive two vaccinations with either 3.75 or 7.5 μg hemagglutinin antigen 21 days apart. Safety, immunogenicity and the influence of seasonal influenza vaccination and antibody cross-reactivity with a seasonal H1N1 strain was assessed.
  
  
  RESULTS
  A single vaccination with either dose induced substantial increases in H1N1 A/California/07/2009 hemagglutination inhibition (HI) and neutralizing (MN) antibody titers in both adult and elderly subjects. A single 7.5 μg dose induced seroprotection rates of 86.9% in adults and 75.2% in elderly subjects. Two 7.5 μg vaccinations induced seroprotection rates in adult and elderly subjects of 90.9% and 89.1%, respectively. The robust immune response to vaccination was confirmed by analyses of neutralizing antibody titers. Both HI and MN antibodies persisted for ≥ 6 months post-vaccination. Between 34% and 49% of subjects had seroprotective levels of H1N1 A/California/07/2009 antibodies at baseline. Higher baseline HI titers were associated with receipt of the 2008-09 or 2009-10 seasonal influenza vaccine. High baseline A/California/07/2009 neutralizing antibody titers were also associated with high baseline titers against A/New Caledonia/20/99, a seasonal H1N1 strain which circulated and was included in the seasonal vaccine from 2000-01 to 2006-07. Pre-adsorption with A/H1N1/New Caledonia/20/99 antigen reduced A/H1N1/California/07/2009 baseline titers in 55% of tested sera. The vaccine was well tolerated with low rates of fever.
  
  
  CONCLUSIONS
  A whole-virus H1N1 A/California/07/2009 vaccine was safe and well tolerated and a single dose induced substantial immune responses similar to seasonal influenza vaccines, probably due to immunological priming by previous seasonal influenza vaccines or infections.
authors.affiliation: Global R&D, Baxter BioScience, Vienna, Austria. hartmut ehrlich@baxter.com
authors.forename: Hartmut J
authors.initials: HJ
authors.lastname: Ehrlich
authors.forename: Markus
authors.initials: M
authors.lastname: Müller
authors.forename: Herwig
authors.initials: H
authors.lastname: Kollaritsch
authors.forename: Fritz
authors.initials: F
authors.lastname: Pinl
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schmitt
authors.forename: Markus
authors.initials: M
authors.lastname: Zeitlinger
authors.forename: Alexandra
authors.initials: A
authors.lastname: Loew-Baselli
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kreil
authors.forename: Otfried
authors.initials: O
authors.lastname: Kistner
authors.forename: Daniel
authors.initials: D
authors.lastname: Portsmouth
authors.forename: Sandor
authors.initials: S
authors.lastname: Fritsch
authors.forename: Friedrich
authors.initials: F
authors.lastname: Maritsch
authors.forename: Gerald
authors.initials: G
authors.lastname: Aichinger
authors.forename: Borislava G
authors.initials: BG
authors.lastname: Pavlova
authors.forename: P Noel
authors.initials: PN
authors.lastname: Barrett
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002522:Chlorocebus aethiops; D003429:Cross Reactions; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000096:biosynthesis / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D014709:Vero Cells; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007252:Influenza Vaccines