title: Immunogenicity and safety of an adjuvanted hepatitis B vaccine in pre-hemodialysis and hemodialysis patients.
abstract: BACKGROUND
  Due to their impaired immune system, patients with renal insufficiency have a suboptimal response to hepatitis B (HB) vaccination and frequent boosters are needed to maintain protection. GlaxoSmithKline Biologicals has developed a HB vaccine containing a new adjuvant system AS04 for use in this immunocompromised patient population.
  
  
  METHODS
  In an open, randomized clinical trial conducted in pre-hemodialysis (documented creatinine clearance < or =30 mL/min) and hemodialysis patients, over 15 years of age and naïve for HB, the immunogenicity and safety of single doses of HB-AS04 (Fendrix, GlaxoSmithKline Biologicals) were compared to double doses of commercially available HB vaccine (Engerix, GlaxoSmithKline Biologicals) administered at 0, 1, 2, and 6 months, and followed-up for 36 months.
  
  
  RESULTS
  The HB-AS04 vaccine elicited a more rapid onset of protection than the currently licensed vaccine for this particular population, with 74% versus 52% of subjects seroprotected at month 3. After the vaccination course, seroprotection rates increased to 91% versus 84% in the HB-AS04 and standard vaccine groups, respectively. Differences persisted up to 36 months post-vaccination (73% vs. 52%, respectively). Antibody concentrations were higher following the HB-AS04 vaccine at all post-vaccination time points. During the follow-up, significantly fewer subjects primed with the HB-AS04 vaccine needed a booster dose as a consequence of anti-HBs loss below seroprotective levels (11/62 subjects in the HB-AS04 group vs. 22/57 subjects in the standard vaccine group, respectively, P = 0.014). The HB-AS04 was more locally reactogenic than the standard immunization regimen, with pain at the injection site occurring with 41% of HB-AS04 doses versus 19% of standard vaccine doses. The occurrence of grade 3 pain was less than 1% in both groups and all events resolved within the 4-day follow-up period.
  
  
  CONCLUSIONS
  The improved immunogenicity profile and clinically acceptable reactogenicity of HB-AS04 vaccine are of key importance to provide a more rapid, enhanced, and longer seroprotection to these immunocompromised patients at risk for HB infection.
authors.affiliation: National University Hospital of Malaysia, Kuala Lumpur.
authors.forename: Norella Kong Chiew
authors.initials: NK
authors.lastname: Tong
authors.forename: Jiri
authors.initials: J
authors.lastname: Beran
authors.forename: Swee Ann
authors.initials: SA
authors.lastname: Kee
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Miguel
authors.forename: Carmen
authors.initials: C
authors.lastname: Sánchez
authors.forename: Jose Maria
authors.initials: JM
authors.lastname: Bayas
authors.forename: A
authors.initials: A
authors.lastname: Vilella
authors.forename: J R
authors.initials: JR
authors.lastname: de Juanes
authors.forename: P
authors.initials: P
authors.lastname: Arrazola
authors.forename: Francisco
authors.initials: F
authors.lastname: Calbo-Torrecillas
authors.forename: Eduardo López
authors.initials: EL
authors.lastname: de Novales
authors.forename: Virginie
authors.initials: V
authors.lastname: Hamtiaux
authors.forename: Marc
authors.initials: M
authors.lastname: Lievens
authors.forename: Michel
authors.initials: M
authors.lastname: Stoffel
mesh_terms: D000276:Adjuvants, Immunologic; D000368:Aged; D005260:Female; D006509:Hepatitis B / Q000276:immunology / Q000517:prevention & control*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D016867:Immunocompromised Host; D007676:Kidney Failure, Chronic / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis
chemical_list: D000276:Adjuvants, Immunologic; D017325:Hepatitis B Vaccines