Results of a phase III clinical trial with an HBsAg-HBIG immunogenic complex therapeutic vaccine for chronic hepatitis B patients: experiences and findings

J Hepatol. 2013 Sep;59(3):450-6. doi: 10.1016/j.jhep.2013.05.003. Epub 2013 May 11.


Background & aims: Even though various experimental therapeutic approaches for chronic hepatitis B infection have been reported, few of them have been verified by clinical trials. We have developed an antigen-antibody (HBsAg-HBIG) immunogenic complex therapeutic vaccine candidate with alum as adjuvant (YIC), aimed at breaking immune tolerance to HBV by modulating viral antigen processing and presentation. A double-blind, placebo-controlled, phase II B clinical trial of YIC has been reported previously, and herein we present the results of the phase III clinical trial of 450 patients.

Methods: Twelve doses of either YIC or alum alone as placebo were administered randomly to 450 CHB patients and they were followed for 24weeks after the completion of immunization. The primary end point was HBeAg seroconversion, and the secondary end points were decrease in viral load, improvement of liver function, and histology.

Results: In contrast to the previous phase II B trial using six doses of YIC and alum as placebo, six more injections of YIC or alum resulted in a decrease of the HBeAg seroconversion rate from 21.8% to 14.0% in the YIC group, but an increase from 9% to 21.9% in the alum group. Decrease in serum HBV DNA and normalization of liver function were similar in both groups (p>0.05).

Conclusions: Overstimulation with YIC did not increase but decreased its efficacy due to immune fatigue in hosts. An appropriate immunization protocol should be explored and is crucial for therapeutic vaccination. Multiple injections of alum alone could have stimulated potent inflammatory and innate immune responses contributing to its therapeutic efficacy, and needs further investigation.

Keywords: Antigen-antibody complex; Chronic hepatitis B; Clinical trial; Phase III; Therapeutic vaccine.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adult
  • Alum Compounds / administration & dosage
  • Antigen-Antibody Complex / administration & dosage
  • Antigen-Antibody Complex / therapeutic use
  • Cytokines / blood
  • Double-Blind Method
  • Female
  • Genotype
  • Hepatitis B Surface Antigens / administration & dosage
  • Hepatitis B Surface Antigens / therapeutic use*
  • Hepatitis B e Antigens / blood
  • Hepatitis B virus / classification
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / pathology
  • Hepatitis B, Chronic / therapy*
  • Humans
  • Immunoglobulins / administration & dosage
  • Immunoglobulins / therapeutic use*
  • Male
  • Viral Vaccines / adverse effects
  • Viral Vaccines / therapeutic use*
  • Young Adult


  • Adjuvants, Immunologic
  • Alum Compounds
  • Antigen-Antibody Complex
  • Cytokines
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Immunoglobulins
  • Viral Vaccines
  • aluminum sulfate
  • hepatitis B hyperimmune globulin