title: Long-term immunogenicity of an AS03-adjuvanted influenza A(H1N1)pdm09 vaccine in young and elderly adults: an observer-blind, randomized trial.
abstract: BACKGROUND
  This study (NCT00979602) evaluated the immunogenicity and relative protective efficacy of one dose of influenza A(H1N1)pdm09 vaccine with or without AS03 (an α-tocopherol oil-in-water emulsion based Adjuvant System).
  
  
  METHODS
  Four thousands and forty-eight healthy adults aged ≥ 18 years were randomized (1:1) to receive one dose of either the adjuvanted split virion (3.75 μg hemagglutinin antigen [HA]/AS03) or non-adjuvanted (15 μg HA) vaccine. Hemagglutination inhibition [HI] antibody response was evaluated before vaccination and at Days 21, 42 and 182 (Month 6). Safety of the study vaccines was evaluated during the entire study duration.
  
  
  RESULTS
  At Day 21, both study vaccines induced HI immune responses meeting the US regulatory criteria in subjects 18-64 years (seroprotection rate [SPR]: 98.0% [97.1-98.6]; seroconversion rate [SCR]: 89.7% [88.0-91.2] in the AS03-adjuvanted group; SPR: 91.4% [89.9-92.8]; SCR: 74.6% [72.3-76.9] in the non-adjuvanted group) and >64 years of age (SPR: 86.0% [82.5-89.0]; SCR: 75.3% [71.1-79.2] in the AS03-adjuvanted group; SPR: 69.1% [64.6-73.3]; SCR: 56.7% [52.0-61.3] in the non-adjuvanted group). The AS03-adjuvanted vaccine induced higher HI geometric mean titers than the non-adjuvanted vaccine at all time points. At Month 6, only subjects 18-64 years of age from both vaccine groups still met the US regulatory criteria (SPR: 82.1% [80.0-84.1]; SCR: 62.3% [59.6-64.8] in the AS03-adjuvanted group; SPR: 75.3% [72.9-77.5]; SCR: 53.7% [51.0-56.4] in the non-adjuvanted group). Protective efficacy was not evaluated due to low number of RT-qPCR-confirmed A(H1N1)pdm09 influenza cases. Through Month 12, 216 serious adverse events (in 157 subjects: 84 in the AS03-adjuvanted and 73 in the non-adjuvanted group) and 12 potentially immune mediated diseases (5 in the AS03-adjuvanted and 7 in the non-adjuvanted group) were reported.
  
  
  CONCLUSIONS
  A single dose of either adjuvanted or non-adjuvanted influenza A(H1N1)pdm09 vaccine induced protective HI antibody levels against the A/California/7/2009 strain that persisted through Month 6 in the 18-64 years population.
authors.affiliation: Allergy and Asthma Research Center and University of Ottawa Medical School, Ottawa, ON, Canada. wyang@yangmedicine.com
authors.forename: William H
authors.initials: WH
authors.lastname: Yang
authors.forename: Marc
authors.initials: M
authors.lastname: Dionne
authors.forename: Michael
authors.initials: M
authors.lastname: Kyle
authors.forename: Naresh
authors.initials: N
authors.lastname: Aggarwal
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Miguel
authors.initials: M
authors.lastname: Madariaga
authors.forename: Olivier
authors.initials: O
authors.lastname: Godeaux
authors.forename: David W
authors.initials: DW
authors.lastname: Vaughn
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation / Q000276:immunology; D004338:Drug Combinations; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control; D008875:Middle Aged; D011136:Polysorbates / Q000008:administration & dosage; D013185:Squalene / Q000008:administration & dosage / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D055815:Young Adult; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D004338:Drug Combinations; D007252:Influenza Vaccines; D011136:Polysorbates; D013185:Squalene; C550253:AS03 adjuvant; D024502:alpha-Tocopherol
keywords: ATP; Adjuvant; BARDA; BMI; Biomedical Advanced Research and Development Authority; CBER; CHMP; CI; Center for Biologics Evaluation & Research; Committee for Medicinal Products for Human Use; GMFR; GMT; H1N1; HA; HHS; HI; ILIs; Influenza; Influenza-Like-Illnesses; Pandemic; RVP; SAEs; SCR; SD; SPR; TVC; United States Department of Health and Human Services; VEI; Vaccine; WHO; World Health Organization; according to protocol; body mass index; confidence interval; geometric mean fold rise; geometric mean titer; hemagglutination inhibition; hemagglutinin; pIMDs; potential immune mediated diseases; respiratory viral panel; serious adverse events; seroconversion rate; seroprotection rate; standard deviation; total vaccinated cohort; vaccine effectiveness improvement