Adjuvanted recombinant HBV vaccine (HBV-AS04) is effective over extended follow-up in dialysis population. An open-label non randomized trial

Clin Res Hepatol Gastroenterol. 2020 Nov;44(6):905-912. doi: 10.1016/j.clinre.2020.01.010. Epub 2020 Mar 3.


Background: Patients on regular dialysis show a poor response to hepatitis B vaccine due to uremia. A recombinant HB vaccine (containing an improved adjuvant system AS04, HBV-AS04) has been licensed but the evidence on its efficacy and safety in dialysis population over the long term is extremely limited.

Aim: We have measured antibody (anti-HBs) persistence for up to 72 months in a large cohort of patients on long-term dialysis (with susceptibility to HBV infection) who underwent vaccination with HBV-AS04 vaccine.

Methods: Patients were prospectively recruited to receive four 20-mcg doses of HBV-AS04 by intramuscular route (deltoid muscle). Two vaccine schedules were adopted: 0,1,2, and 3 month (n=217 patients) and 0,1,2, and 6 month (n=31 patients). Anti-HBs antibody concentrations were tested at 1,2,3, 4, 7 and 12 months and then every year up to 72 months. Multivariate analysis was made to find the baseline parameters that were associated with the immune response to HBV-AS04 vaccine.

Results: Two hundred and seventy-two patients were included and 248 completed the study. At completion of vaccine schedule, the frequency of responders (anti-HBs titers≥10mIU/mL) was 81.5% (202/248) (mean anti-HBs antibody titers, 384.9±391.9mIU/mL), according to per-protocol analysis. On the grounds of univariate analysis, age was lower in responder than non- responder patients to HBV AS04 even if no statistical significance was achieved (P=0.09). The sero-protection rate at month 72 was 77% (7/9) (anti-HBs antibody titers, 184.9±360.1mIU/mL, P=0.001). Multivariate analysis found a relationship between sero-response rate and age (P=0.04). No major side effects and no de novo HBV episodes were observed.

Conclusions: Our open-label nonrandomized trial performed in a 'real-world' practice showed the persistence of anti-HBs antibody among responder patients over a very long follow-up. Studies with longer observation periods are under way.

Keywords: Adjuvant; Dialysis; Follow-up; Hepatitis B vaccine; Immunogenicity.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Age Factors
  • Aged
  • Female
  • Hepatitis B Antibodies / blood
  • Hepatitis B Vaccines*
  • Humans
  • Immunogenicity, Vaccine
  • Male
  • Prospective Studies
  • Renal Dialysis*
  • Renal Insufficiency, Chronic / therapy
  • Vaccines, Synthetic*


  • Hepatitis B Antibodies
  • Hepatitis B Vaccines
  • Vaccines, Synthetic