title: Immunogenicity and safety of AS03A-adjuvanted H5N1 influenza vaccine prepared from bulk antigen after stockpiling for 4 years.
abstract: BACKGROUND
  Stockpiling vaccine for deployment in the event of an influenza pandemic is an important mitigation strategy. A necessary aspect of stockpiling is to determine the shelf-life of the stored vaccine.
  
  
  METHODS
  In this Phase II, open-label study we assessed the immunogenicity and safety of H5N1 A/Indonesia/5/2005 vaccine adjuvanted with AS03A. The AS03A-H5N1 vaccine was prepared from bulk antigen that had been stored for 4 years, and adjuvant that had been stored for 2.5 years. Both the antigen and adjuvant were filled in separate multi-dose vials within 4 months of use, and on the day of vaccination, the contents of antigen and adjuvant vials were mixed. Seventy-eight adults aged 18-64 years were scheduled to receive two doses of hemagglutinin-antigen (3.75μg) given 21 days apart. Antibody responses were assessed by hemagglutination-inhibition (HI) assay according to age (18-30 years, 31-40 years, 41-50 years, and 51-64 years). Reactogenicity was assessed for 7 days after each vaccination, and safety was assessed for 385 days post-vaccination (NCT01416571).
  
  
  RESULTS
  The vaccine was immunogenic. Twenty-one days after the second dose of vaccine in the overall population, the HI seroconversion rate and seroprotection rate (SPR; titer ≥1:40) was 96.0% and 98.7%, respectively. At Day 182 after vaccination, the SPR was 76.7% in the overall population. Injection site pain was the most frequent solicited adverse event (91.0%), and no safety concerns were raised.
  
  
  CONCLUSIONS
  The immunogenicity and safety observed with AS03A-H5N1 vaccine formulated with bulk antigen which had been stockpiled before vialing and administration was consistent with that previously observed with newly manufactured AS03A-H5N1 vaccine. This suggests that stockpiling bulk antigen for 4 years does not compromise the immunogenicity or reactogenicity of the vaccine.
authors.affiliation: GlaxoSmithKline Vaccines, Wavre, Belgium. Electronic address: olivier.o.godeaux@gsk.com.
authors.forename: Olivier
authors.initials: O
authors.lastname: Godeaux
authors.affiliation: GlaxoSmithKline Vaccines, Wavre, Belgium.
authors.forename: Patricia
authors.initials: P
authors.lastname: Izurieta
authors.affiliation: Naples Community Hospital, Naples, FL, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Madariaga
authors.affiliation: GlaxoSmithKline Vaccines, King of Prussia, PA, USA.
authors.forename: Mamadou
authors.initials: M
authors.lastname: Dramé
authors.affiliation: GlaxoSmithKline Vaccines, King of Prussia, PA, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: GlaxoSmithKline Vaccines, Rixensart, Belgium.
authors.forename: David W
authors.initials: DW
authors.lastname: Vaughn
mesh_terms: D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; 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*; D008297:Male; D008875:Middle Aged; D000069078:Seroconversion; D062205:Strategic Stockpile / Q000592:standards*; D013997:Time Factors; D014611:Vaccination; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines
keywords: AS03; Bulk antigen; H5N1 vaccine; Pandemic influenza; Stockpile