title: Safety and immunogenicity of influenza A H5 subunit vaccines: effect of vaccine schedule and antigenic variant.
abstract: BACKGROUND
  The current US national stockpile of influenza H5 vaccine was produced using the antigen from the strain A/Vietnam/1203/2004 (a clade 1 H5 virus). Recent H5 disease has been caused by antigenically divergent H5 viruses, including A/Indonesia/05/2005 (a clade 2 H5 virus).
  
  
  METHODS
  The influence of schedule on the antibody response to 2 doses of H5 vaccines (one a clade 1 hemagglutinin protein [HA] vaccine and one a clade 2 HA vaccine) containing 90 μg of antigen was evaluated in healthy adults 18-49 years of age.
  
  
  RESULTS
  Two doses of vaccine were required to induce antibody titers ≥ 1:10 in most subjects. Accelerated schedules were immunogenic, and antibody developed after vaccinations on days 0 and 7, 0 and 14, and 0 and 28, with the day 0 and 7 schedule inducing lower titers than those induced with the other schedules. With mixed vaccine schedules of clade 1 followed by clade 2 vaccine administration, the first vaccination primed for a heterologous boost. The heterologous response was improved when the second vaccination was given 6 months after the first, compared with the response when the second vaccination was given after an interval of 1 month.
  
  
  CONCLUSIONS
  An accelerated vaccine schedule of injections administered at days 0 and 14 was as immunogenic as a vaccine schedule of injections at days 0 and 28, but both schedules were inferior to a vaccine schedule of injections administered at 0 and 6 months for priming for heterologous vaccine boosting. Clinical Trial Registry Number: NCT00703053.
authors.affiliation: Division of Infectious Diseases and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri 63104, USA. belsherb@slu.edu
authors.forename: Robert B
authors.initials: RB
authors.lastname: Belshe
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Frey
authors.forename: Irene
authors.initials: I
authors.lastname: Graham
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Mulligan
authors.forename: Srilatha
authors.initials: S
authors.lastname: Edupuganti
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Jackson
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
authors.forename: Gregory
authors.initials: G
authors.lastname: Poland
authors.forename: Robert
authors.initials: R
authors.lastname: Jacobson
authors.forename: Harry L
authors.initials: HL
authors.lastname: Keyserling
authors.forename: Paul
authors.initials: P
authors.lastname: Spearman
authors.forename: Heather
authors.initials: H
authors.lastname: Hill
authors.forename: Mark
authors.initials: M
authors.lastname: Wolff
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D000940:Antigenic Variation; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000592:standards; D007251:Influenza, Human / Q000097:blood / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000592:standards; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D022223:Vaccines, Subunit