title: Assessment of the safety, tolerability and kinetics of the immune response to A/H1N1v vaccine formulations with and without adjuvant in healthy pediatric subjects from 3 through 17 years of age.
abstract: BACKGROUND
  The recent global A/H1N1v pandemic led to major efforts to develop effective vaccines against the novel virus, while global demand and limited production capacity focused attention on dose sparing and schedules.
  
  
  METHODS
  An open-label phase III study of immunogenicity and safety of novel A/H1N1v vaccines included 392 Costa Rican children in two pediatric cohorts (3-8 and 9-17 years). They received two doses, of either an MF59®-adjuvanted formulation containing 7.5 μg antigen or non-adjuvanted formulations containing 15 or 30 μg antigen, three weeks apart. Immunogenicity was assessed as hemagglutination inhibition (HI) titers using the CBER licensure criteria.
  
  
  RESULTS
  All three vaccines elicited immune responses in 9-17 year-olds meeting CBER criteria three weeks after one dose; responses were not enhanced by second dose. In 3-8 year-olds only the adjuvanted vaccine met the CBER criteria after one dose, but all three vaccines met criteria after second dose. All vaccines were well tolerated; no related Serious Adverse Events (SAE) and few severe solicited reactions were reported. MF59-adjuvanted vaccine was associated with more reports of injection site pain and tenderness and overall systemic solicited reactions, most notably in older subjects, all of which decreased after the second dose.
  
  
  CONCLUSIONS
  One dose of non-adjuvanted A/H1N1v vaccine is adequate in 9-17 year-olds, but younger children require either one dose of MF59-adjuvanted vaccine or two doses of non-adjuvanted vaccine to achieve protective titers. Enhanced immunogenicity with MF59 is associated with a small increase in reactogenicity, but no safety issues.
authors.affiliation: Instituto de Atención Pediátrica, San José, Costa Rica.
authors.forename: Adriano
authors.initials: A
authors.lastname: Arguedas
authors.forename: Carolina
authors.initials: C
authors.lastname: Soley
authors.forename: Arturo
authors.initials: A
authors.lastname: Abdelnour
authors.forename: Victor
authors.initials: V
authors.lastname: Sales
authors.forename: Kelly
authors.initials: K
authors.lastname: Lindert
authors.forename: Giovanni
authors.initials: G
authors.lastname: Della Cioppa
authors.forename: Ralf
authors.initials: R
authors.lastname: Clemens
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000367:Age Factors; D000914:Antibodies, Viral / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D011136:Polysorbates / Q000008:administration & dosage; D013185:Squalene / Q000008:administration & dosage; D014611:Vaccination / Q000379:methods
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D013185:Squalene