title: Immunogenicity and safety of an AS03(A)-adjuvanted H5N1 influenza vaccine in a Taiwanese population.
abstract: OBJECTIVE
  A multicenter study (NCT00449670) conducted across Taiwan, Singapore, Hong Kong and Thailand evaluated the safety and manufacturing consistency of four formulations of an AS03(A)-adjuvanted H5N1 vaccine in terms of immune response against the vaccine-homologous strain (A/Vietnam/1194/2004). This manuscript presents data from the Taiwanese population.
  
  
  METHODS
  A total of 400 individuals, aged 18-60 years, were randomized into six groups (2:2:2:2:1:1 ratio) to receive two doses (21 days apart) of one of the four adjuvanted formulations (H5N1-AS03(A)-groups) or one of the two nonadjuvanted formulations (H5N1-DIL-groups). Blood samples collected before vaccination (Day 0) and 21 days after each vaccine dose were analyzed using hemagglutination inhibition (HI) assay. Adverse events were recorded.
  
  
  RESULTS
  All four AS03(A)-adjuvanted formulations induced comparable immune responses against the A/Vietnam/1194/2004 strain; following the second dose, immune response in terms of HI antibodies was higher in the H5N1-AS03(A)-groups {seroprotection rate=91.6% [95% confidence interval (CI): 87.9-94.4]; geometric mean titer (GMT)=177.6 (95% CI: 153.2-206.0)} compared with the H5N1-DIL-groups [seroprotection rates=5.0% (95% CI: 1.4-12.3); GMT=6.3 (95% CI: 5.4-7.4)]. Immune response against the heterologous A/Indonesia/05/2005 strain was also stronger in the H5N1-AS03(A)-groups [seroprotection rate=45.6% (95% CI: 40.0-51.4); GMT=20.5 (95% CI: 17.8-23.7)] compared with the H5N1-DIL groups [seroprotection rate=0.0% (95% CI: 0.0-4.5); GMT=5.0 (95% CI: 5.0-5.0)]. The overall reactogenicity profile of the adjuvanted formulations was clinically acceptable.
  
  
  CONCLUSIONS
  The AS03(A)-adjuvanted H5N1 influenza vaccine formulations induced stronger immune response against the vaccine-homologous and heterologous strains than the nonadjuvanted formulations. The AS03(A)-adjuvanted H5N1 vaccine demonstrated a good immunogenicity and an acceptable safety profile in the Taiwanese population.
authors.affiliation: Taipei Veterans General Hospital, 201 Section 2, Shih-Pai Road, and National Yang Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Shinn-Jang
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Shan-Chwen
authors.initials: SC
authors.lastname: Chang
authors.forename: Chong-Jen
authors.initials: CJ
authors.lastname: Yu
authors.forename: Yu-Jiun
authors.initials: YJ
authors.lastname: Chan
authors.forename: Tzeng-Ji
authors.initials: TJ
authors.lastname: Chen
authors.forename: Shie-Liang
authors.initials: SL
authors.lastname: Hsieh
authors.forename: Hsiu-Yun
authors.initials: HY
authors.lastname: Lai
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Lin
authors.forename: Jui-Yao
authors.initials: JY
authors.lastname: Liu
authors.forename: Gary
authors.initials: G
authors.lastname: Ong
authors.forename: Francois
authors.initials: F
authors.lastname: Roman
authors.forename: Mamadou
authors.initials: M
authors.lastname: Dramé
authors.forename: Hans L
authors.initials: HL
authors.lastname: Bock
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013624:Taiwan; D024505:Tocopherols / Q000008:administration & dosage
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D024505:Tocopherols