Viral Hepatitis
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Nov 28, 2007; 13(44): 5911-5917
Published online Nov 28, 2007. doi: 10.3748/wjg.v13.i44.5911
Targeting hepatitis B virus antigens to dendritic cells by heat shock protein to improve DNA vaccine potency
Qin-Long Gu, Xue Huang, Wen-Hong Ren, Lei Shen, Bing-Ya Liu, Si-Yi Chen
Qin-Long Gu, Bing-Ya Liu, Department of Surgery, Shanghai Institute of Digestive Surgery, Affiliated Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Xue Huang, Wen-Hong Ren, Lei Shen, Si-Yi Chen, Center for Cell and Gene Therapy, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, United States
Author contributions: All authors contributed equally to the work.
Correspondence to: Dr. Qin-Long Gu, Department of Surgery, Shanghai Institute of Digestive Surgery, Affiliated Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 227 Chongqing Nan Road, Shanghai 200025, China. qlgu@shsmu.edu.cn
Telephone: +86-21-63841391 Fax: +86-21-63842157
Received: June 5, 2007
Revised: September 5, 2007
Accepted: October 22, 2007
Published online: November 28, 2007
Abstract

AIM: To investigate a novel DNA vaccination based upon expression of the HBV e antigen fused to a heat shock protein (HSP) as a strategy to enhance DNA vaccine potency.

METHODS: A pCMV-HBeAg-HSP DNA vaccine and a control DNA vaccine were generated. Mice were immunized with these different construct. Immune responses were measured 2 wk after a second immunization by a T cell response assay, CTL cytotoxicity assay, and an antibody assay in C57BL/6 and BALB/c mice. CT26-HBeAg tumor cell challenge test in vivo was performed in BALB/c mice to monitor anti-tumor immune responses.

RESULTS: In the mice immunized with pCMV-HBe-HSP DNA, superior CTL activity to target HBV-positive target cells was observed in comparison with mice immunized with pCMV-HBeAg (44% ± 5% vs 30% ± 6% in E: T > 50:1, P < 0.05). ELISPOT assays showed a stronger T-cell response from mice immunized with pCMV-HBe-HSP than that from pCMV-HBeAg immunized animals when stimulated either with MHC classIor class II epitopes derived from HBeAg (74% ± 9% vs 31% ± 6%, P < 0.01). ELISA assays revealed an enhanced HBeAg antibody response from mice immunized with pCMV-HBe-HSP than from those immunized with pCMV-HBeAg. The lowest tumor incidence and the slowest tumor growth were observed in mice immunized with pCMV-HBe-HSP when challenged with CT26-HBeAg.

CONCLUSION: The results of this study demonstrate a broad enhancement of antigen-specific CD4+ helper, CD8+ cytotoxic T-cell, and B-cell responses by a novel DNA vaccination strategy. They also proved a stronger antigen-specific immune memory, which may be superior to currently described HBV DNA vaccination strategies for the treatment of chronic HBV infection.

Keywords: Hepatitis B virus antigen, Dendritic cell, Heat shock protein, DNA vaccine