title: Results of a phase III clinical trial with an HBsAg-HBIG immunogenic complex therapeutic vaccine for chronic hepatitis B patients: experiences and findings.
abstract: OBJECTIVE
  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.
authors.affiliation: Beijing Ditan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Dao-Zhen
authors.initials: DZ
authors.lastname: Xu
authors.forename: Xuan-Yi
authors.initials: XY
authors.lastname: Wang
authors.forename: Xin-Liang
authors.initials: XL
authors.lastname: Shen
authors.forename: Guo-Zhong
authors.initials: GZ
authors.lastname: Gong
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Guo
authors.forename: Ai-Min
authors.initials: AM
authors.lastname: Sun
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.forename: Lan-Juan
authors.initials: LJ
authors.lastname: Li
authors.forename: Xin-Hui
authors.initials: XH
authors.lastname: Guo
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhen
authors.forename: Hui-Fen
authors.initials: HF
authors.lastname: Wang
authors.forename: Huan-Yu
authors.initials: HY
authors.lastname: Gong
authors.forename: Cheng
authors.initials: C
authors.lastname: Xu
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.forename: Chen
authors.initials: C
authors.lastname: Pan
authors.forename: Zuo-Jiong
authors.initials: ZJ
authors.lastname: Gong
authors.forename: Ji-Ming
authors.initials: JM
authors.lastname: Zhang
authors.forename: Jia
authors.initials: J
authors.lastname: Shang
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.forename: Tie-Feng
authors.initials: TF
authors.lastname: Wu
authors.forename: Wen-Xiang
authors.initials: WX
authors.lastname: Huang
authors.forename: Yong-Guo
authors.initials: YG
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Zheng-Hong
authors.initials: ZH
authors.lastname: Yuan
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Wen
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D000534:Alum Compounds / Q000008:administration & dosage; D000936:Antigen-Antibody Complex / Q000008:administration & dosage / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage / Q000627:therapeutic use*; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007136:Immunoglobulins / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D014765:Viral Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000936:Antigen-Antibody Complex; D016207:Cytokines; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D007136:Immunoglobulins; D014765:Viral Vaccines; C041524:aluminum sulfate; C045213:hepatitis B hyperimmune globulin
keywords: Antigen-antibody complex; Chronic hepatitis B; Clinical trial; Phase III; Therapeutic vaccine