title: Assessment of Prime-boost Vaccination Using an AS03B-adjuvanted Influenza A (H5N1) Vaccine: A Randomized Trial in Children of Three to Less Than Eighteen Years of Age.
abstract: BACKGROUND
  Heterologous prime-boost vaccination is a pandemic response strategy utilizing subtype-matched vaccine at pandemic onset followed by strain-matched vaccine once available. Persistence of immune response and safety of influenza A (H5N1) vaccine adjuvanted with adjuvant system containing α-tocopherol and squalene in an oil-in-water emulsion (AS03B) were evaluated.
  
  
  METHODS
  An open phase 3 active-controlled study (www.clinicaltrials.gov NCT01379937) assessed immunogenicity and reactogenicity of a heterologous booster dose of A/turkey/Turkey/1/2005-H5N1-AS03B in children 3 to <18 years of age, given 6 months after 2-dose priming with A/Indonesia/05/2005-H5N1-AS03B (H5N1(2) -H5N1 group) compared with a single dose of A/turkey/Turkey/1/2005-H5N1-AS03B in unprimed subjects (hepatitis A vaccine (HAV)-H5N1 group). Hemagglutinin inhibition responses and microneutralization antibodies were assessed to 6 months after booster vaccination.
  
  
  RESULTS
  Hemagglutinin inhibition antibody responses against A/turkey/Turkey/1/2005-H5N1 were superior in the H5N1(2)-H5N1 versus the hepatitis A vaccine-H5N1 group overall and in each age strata (3 to <10 and 10 to <18 years). Anamnestic immune responses were demonstrated against vaccine-homologous/heterologous strains in the H5N1(2)-H5N1 group. Injection site pain and fever increased with consecutive doses for children <6 years (H5N1(2)-H5N1). Immune responses to vaccine-homologous/heterologous strains persisted to 6 months after booster vaccination in the H5N1(2)-H5N1 group.
  
  
  CONCLUSIONS
  Heterologous H5N1-AS03B-adjuvanted booster vaccination in children/adolescents was immunogenic for vaccine-homologous and heterologous strains following 2-dose priming, with immune persistence for at least 6 months. Prime-boost strategies using H5N1-AS03 could be effectively employed in this age group.
authors.affiliation: From the *GSK Vaccines, Wavre, Belgium; †Research Institute for Tropical Medicine, Muntinlupa City, Philippines; and ‡GSK Vaccines, King of Prussia, Pennsylvania.
authors.forename: Patricia
authors.initials: P
authors.lastname: Izurieta
authors.forename: Mercy Jeane
authors.initials: MJ
authors.lastname: Uy-Aragon
authors.forename: Mamadou
authors.initials: M
authors.lastname: Dramé
authors.forename: David W
authors.initials: DW
authors.lastname: Vaughn
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007114:Immunization / Q000379:methods*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D009500:Neutralization Tests; D011136:Polysorbates / Q000008:administration & dosage* / Q000009:adverse effects; D013185:Squalene / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D024502:alpha-Tocopherol / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D004338:Drug Combinations; D007252:Influenza Vaccines; D011136:Polysorbates; D013185:Squalene; C550253:AS03 adjuvant; D024502:alpha-Tocopherol