title: Immunogenicity and Safety of H5N1 A/Vietnam/1194/2004 (Clade 1) AS03-adjuvanted prepandemic candidate influenza vaccines in children aged 3 to 9 years: a phase ii, randomized, open, controlled study.
abstract: BACKGROUND
  The development of vaccines against pandemic influenza viruses for use in children is a public health priority.
  
  
  METHODS
  In this phase II, randomized, open study, the immunogenicity and reactogenicity of H5N1 A/Vietnam/1194/2004 (NIBRG-14) (clade 1) prepandemic influenza vaccine were assessed in children aged 3 to 5 and 6 to 9 years. Children were randomized to receive 2 doses, given 21 days apart, of A/Vietnam/1194/2004 vaccine containing 1.9 microg or 3.75 microg hemagglutinin antigen (HA), adjuvanted with a tocopherol-based oil-in-water emulsion (AS03) containing 11.86 mg (AS03(A)) or 5.93 mg (AS03(B)) tocopherol. Control groups received 2 doses of trivalent influenza vaccine (TIV). Humoral immune responses, reactogenicity, and safety were the primary outcome measures; cross-reactivity and cell-mediated responses were also assessed (NCT00502593).
  
  
  RESULTS
  Between 49 and 51 children in each age stratum (aged 3-5 and 6-9 years) received H5N1 vaccine, and between 17 and 18 children in each age stratum received TIV. After the second dose, recipients of H5N1 vaccine (1.9 microg HA/AS03(B), 3.75 microg HA/AS03(B), and 3.75 microg HA/AS03(A)) achieved humoral antibody titers against the vaccine-homologous strain, which fulfilled the United States influenza vaccines licensure criteria for immunogenicity. With the exception of 1 child, there were no H5N1 immune responses in children who received TIV. The most frequent injection-site event was pain in all groups, and the H5N1 vaccine had a clinically acceptable reactogenicity and safety profile. Exploratory analyses in children aged 3 to 5 years indicated that the induction of CD4 T-cell responses polarized in favor of a T-helper 1 profile.
  
  
  CONCLUSIONS
  The results showed that 2 doses of AS03-adjuvanted H5N1 influenza vaccine at antigen-sparing doses of 1.9 microg or 3.75 microg HA elicited broad and persistent immune responses with acceptable reactogenicity, and without safety concerns, in children aged 3 to 9 years.
authors.affiliation: Centro Superior de Investigación en Salud Pública (CSISP), Area de investigación en Vacunas, Valencia, Spain. diez_jav@gva.es
authors.forename: Javier
authors.initials: J
authors.lastname: Díez-Domingo
authors.forename: Maria
authors.initials: M
authors.lastname: Garcés-Sanchez
authors.forename: José-María
authors.initials: JM
authors.lastname: Baldó
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Planelles
authors.forename: Isabel
authors.initials: I
authors.lastname: Ubeda
authors.forename: Angels
authors.initials: A
authors.lastname: JuBert
authors.forename: Josep
authors.initials: J
authors.lastname: Marés
authors.forename: Philippe
authors.initials: P
authors.lastname: Moris
authors.forename: Pilar
authors.initials: P
authors.lastname: Garcia-Corbeira
authors.forename: Mamadou
authors.initials: M
authors.lastname: Dramé
authors.forename: Paul
authors.initials: P
authors.lastname: Gillard
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004196:Disease Outbreaks / Q000517:prevention & control; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D008297:Male; D009500:Neutralization Tests
chemical_list: D000276:Adjuvants, Immunologic; D007252:Influenza Vaccines