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

被引：167

作者：

Xu, Dao-Zhen ^{[1
]}

Wang, Xuan-Yi ^{[2
]}

Shen, Xin-Liang ^{[3
]}

Gong, Guo-Zhong ^{[4
]}

Ren, Hong ^{[5
]}

Guo, Li-Min ^{[1
]}

Sun, Ai-Min ^{[6
]}

Xu, Min ^{[7
]}

Li, Lan-Juan ^{[8
]}

Guo, Xin-Hui ^{[9
]}

Zhen, Zhen ^{[10
]}

Wang, Hui-Fen ^{[11
]}

Gong, Huan-Yu ^{[12
]}

Xu, Cheng ^{[13
]}

Jiang, Nan ^{[14
]}

Pan, Chen ^{[15
]}

Gong, Zuo-Jiong ^{[16
]}

Zhang, Ji-Ming ^{[17
]}

Shang, Jia ^{[18
]}

Xu, Jie ^{[19
]}

Xie, Qing ^{[20
]}

Wu, Tie-Feng ^{[21
]}

Huang, Wen-Xiang ^{[22
]}

Li, Yong-Guo ^{[23
]}

Xu, Jing ^{[3
]}

Yuan, Zheng-Hong ^{[2
]}

Wang, Bin ^{[2
]}

Zhao, Kai ^{[3
]}

Wen, Yu-Mei ^{[2
]}

Team, Yic Efficacy Trial Study

机构：

[1] Capital Med Univ, Beijing Ditan Hosp, Beijing, Peoples R China

[2] Fudan Univ, Shanghai Med Coll, Key Lab Med Mol Virol, MoE MoH, Shanghai 200032, Peoples R China

[3] Natl Vaccine & Serum Inst, Beijing, Peoples R China

[4] Cent S Univ, Xiangya Hosp 2, Changsha, Hunan, Peoples R China

[5] Chongqing Med Univ, Affiliated Hosp 2, Chongqing, Peoples R China

[6] Inst Med Sci, Zhengzhou, Henan, Peoples R China

[7] Guangzhou Eight Peoples Hosp, Guangzhou, Guangdong, Peoples R China

[8] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Hangzhou, Peoples R China

[9] Capital Med Univ, Beijing Youan Hosp, Beijing, Peoples R China

[10] Hebei Med Univ, Hosp 3, Shijiazhuang, Peoples R China

[11] Beijing 302 Hosp, Beijing, Peoples R China

[12] Cent S Univ, Xiangya Hosp 3, Changsha, Hunan, Peoples R China

[13] Shenzhen Donghu Hosp, Shenzhen, Peoples R China

[14] Peoples Hosp Sichuan Prov, Chengdu, Peoples R China

[15] Fuzhou Infect Dis Hosp, Fuzhou, Peoples R China

[16] Wuhan Univ, Peoples Hosp, Wuhan 430072, Peoples R China

[17] Fudan Univ, Huashan Hosp, Shanghai 200433, Peoples R China

[18] Henan Prov Peoples Hosp, Zhenzhou, Peoples R China

[19] Jiao Tong Univ, Peoples Hosp 3, Shanghai 200030, Peoples R China

[20] Jiao Tong Univ, Ruijin Hosp, Shanghai 200030, Peoples R China

[21] Hangzhou Sixth Peoples Hosp, Hangzhou, Zhejiang, Peoples R China

[22] Chongqing Med Univ, Affiliated Hosp 1, Chongqing, Peoples R China

[23] Harbin Med Univ, Affiliated Hosp 1, Harbin, Peoples R China

来源：

JOURNAL OF HEPATOLOGY | 2013年 / 59卷 / 03期

关键词：

Phase III; Clinical trial; Therapeutic vaccine; Chronic hepatitis B; Antigen-antibody complex; E-ANTIGEN SEROCONVERSION; DENDRITIC CELL; HBEAG SEROCONVERSION; IMMUNE-RESPONSES; VIRUS INFECTION; ALUMINUM; DNA; LAMIVUDINE; MECHANISM; ADJUVANTS;

D O I：

10.1016/j.jhep.2013.05.003

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

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 24 weeks 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. (C) 2013 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.

引用

页码：450 / 456

页数：7

共 29 条

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