Immunogenicity and safety of an adjuvanted hepatitis B vaccine in pre-hemodialysis and hemodialysis patients.
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.
Tong
Norella Kong Chiew
NK
National University Hospital of Malaysia, Kuala Lumpur.
Beran
Jiri
J
Kee
Swee Ann
SA
Miguel
Jose Luis
JL
Sánchez
Carmen
C
Bayas
Jose Maria
JM
Vilella
A
A
de Juanes
J R
JR
Arrazola
P
P
Calbo-Torrecillas
Francisco
F
de Novales
Eduardo López
EL
Hamtiaux
Virginie
V
Lievens
Marc
M
Stoffel
Michel
M
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
D000276:Adjuvants, Immunologic; D017325:Hepatitis B Vaccines