title: Long-term booster schedules with AS03A-adjuvanted heterologous H5N1 vaccines induces rapid and broad immune responses in Asian adults.
abstract: BACKGROUND
  The pandemic potential of avian influenza A/H5N1 should not be overlooked, and the continued development of vaccines against these highly pathogenic viruses is a public health priority.
  
  
  METHODS
  This open-label extension booster study followed a Phase III study of 1206 adults who had received two 3.75 μg doses of primary AS03A-adjuvanted or non-adjuvanted H5N1 split-virus vaccine (A/Vietnam/1194/2004; clade 1) (NCT00449670). The aim of the extension study was to evaluate different timings for heterologous AS03A-adjuvanted booster vaccination (A/Indonesia/5/2005; clade 2.1) given at Month 6, 12, or 36 post-primary vaccination. Immunogenicity was assessed 21 days after each booster vaccination and the persistence of immune responses against the primary vaccine strain (A/Vietnam) and the booster strain (A/Indonesia) was evaluated up to Month 48 post-primary vaccination. Reactogenicity and safety were also assessed.
  
  
  RESULTS
  After booster vaccination given at Month 6, HI antibody responses to primary vaccine, and booster vaccine strains were markedly higher with one dose of AS03A-H5N1 booster vaccine in the AS03A-adjuvanted primary vaccine group compared with two doses of booster vaccine in the non-adjuvanted primary vaccine group. HI antibody responses were robust against the primary and booster vaccine strains 21 days after boosting at Month 12 or 36. At Month 48, in subjects boosted at Month 6, 12, or 36, HI antibody titers of ≥1:40 against the booster strain persisted in 39.2%, 61.2%, and 95.6% of subjects, respectively. Neutralizing antibody responses and cell-mediated immune responses also showed that AS03A-H5N1 heterologous booster vaccination elicited robust immune responses within 21 days of boosting at Month 6, 12, or 36 post-primary vaccination. The booster vaccine was well tolerated, and no safety concerns were raised.
  
  
  CONCLUSIONS
  In Asian adults primed with two doses of AS03A-adjuvanted H5N1 pandemic influenza vaccine, strong cross-clade anamnestic antibody responses were observed after one dose of AS03A-H5N1 heterologous booster vaccine given at Month 6, 12, or 36 after priming, suggesting that AS03A-adjuvanted H5N1 vaccines may provide highly flexible prime-boost schedules. Although immunogenicity decreased with time, vaccinated populations could potentially be protected for up to three years after vaccination, which is likely to far exceed the peak of the a pandemic.
authors.affiliation: GlaxoSmithKline Vaccines, Wavre, Belgium. paul.gillard@gsk.com.
authors.forename: Paul
authors.initials: P
authors.lastname: Gillard
authors.forename: Daniel Wai Sing
authors.initials: DW
authors.lastname: Chu
authors.forename: Shinn-Jang
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
authors.forename: Prasert
authors.initials: P
authors.lastname: Thongcharoen
authors.forename: Fong Seng
authors.initials: FS
authors.lastname: Lim
authors.forename: Mamadou
authors.initials: M
authors.lastname: Dramé
authors.forename: Karl
authors.initials: K
authors.lastname: Walravens
authors.forename: François
authors.initials: F
authors.lastname: Roman
mesh_terms: D000328:Adult; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D044466:Asian People; D003429:Cross Reactions / Q000276:immunology; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011136:Polysorbates / Q000008:administration & dosage* / Q000009:adverse effects; D013185:Squalene / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D055815:Young Adult; D024502:alpha-Tocopherol / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004338:Drug Combinations; D007252:Influenza Vaccines; D011136:Polysorbates; D013185:Squalene; C550253:AS03 adjuvant; D024502:alpha-Tocopherol