title: Rapid immunization against H5N1: a randomized trial evaluating homologous and cross-reactive immune responses to AS03(A)-adjuvanted vaccination in adults.
abstract: BACKGROUND
  Accelerated immunization schedules may help gain early control of influenza pandemics. We investigated different schedules of an AS03(A)-adjuvanted H5N1 vaccine.
  
  
  METHODS
  This phase II, open-label, 6-month study randomized participants (aged 18-64 years) to 2 vaccine doses administered 21 (standard schedule), 14, or 7 days apart, or on the same day. Coprimary end points were that the lower limit of the 98.75% confidence interval 14 days after the last dose must be (1) >40% for seroconversion rate (SCR) (Center for Biologics Evaluation and Research [CBER] criterion) and (2) >50% for seroprotection rate (SPR) (attainment rate for reciprocal hemagglutination inhibition titers ≥40, protocol-defined criterion) for the vaccine homologous strain (A/Indonesia/5/2005). European Committee for Human Medicinal Products (CHMP) immunogenicity criteria were also evaluated.
  
  
  RESULTS
  Coprimary end points were achieved (lower 98.75% confidence intervals exceeded defined values). Titers were highest with the standard schedule. Nevertheless, CBER SCR, protocol-defined SPR, and CHMP criteria were met with all schedules for the A/Indonesia/5/2005 strain. There were no significant differences between age groups (18-40 vs 41-64 years). Immune response was robust against drift variants A/turkey/Turkey/1/2005 and A/Vietnam/1194/2004.
  
  
  CONCLUSIONS
  The AS03(A)-adjuvanted H5N1 vaccine in accelerated schedules offers a robust immune response against vaccine homologous and drift variant strains, allowing consideration of compressed vaccination intervals.
  
  
  BACKGROUND
  NCT00695669.
authors.affiliation: Manna Research, Toronto, Canada.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lasko
authors.forename: Dennis
authors.initials: D
authors.lastname: Reich
authors.forename: Anuradha
authors.initials: A
authors.lastname: Madan
authors.forename: François
authors.initials: F
authors.lastname: Roman
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: Vaughn
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D007252:Influenza Vaccines