Results of a phase III clinical trial with an HBsAg-HBIG immunogenic complex
therapeutic vaccine for chronic hepatitis B patients: experiences and findings.
Author(s): Xu DZ(1), Wang XY, Shen XL, Gong GZ, Ren H, Guo LM, Sun AM, Xu M, Li LJ, Guo XH,
Zhen Z, Wang HF, Gong HY, Xu C, Jiang N, Pan C, Gong ZJ, Zhang JM, Shang J, Xu J,
Xie Q, Wu TF, Huang WX, Li YG, Xu J, Yuan ZH, Wang B, Zhao K, Wen YM; YIC
Efficacy Trial Study Team.
Collaborators: Lei JH, Jiang YF, Hu P, Zhang T, Yang HY, Cao Y, Yan D, Wu W, Li
XM, Hu JH, Zhang HY, Shu D, Yang XX, Zheng L, Yan SN, Wang FL, Zhao L, Shi DM,
Guo XF, Lan YH, Ma ZM, Yao X, Xu LF, Zhang YT, Wu G, Shan P.
Affiliation(s): Author information:
(1)Beijing Ditan Hospital, Capital Medical University, Beijing, People's Republic of
China.
Publication date & source: 2013, J Hepatol. , 59(3):450-6
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.
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