Brief Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jan 28, 2012; 18(4): 349-355
Published online Jan 28, 2012. doi: 10.3748/wjg.v18.i4.349
Adenovirus-expressed preS2 antibody inhibits hepatitis B virus infection and hepatic carcinogenesis
Qian Zhang, Zhi-Qing Li, Hu Liu, Jia-He Yang
Qian Zhang, Department of Infectious Diseases, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
Zhi-Qing Li, Hu Liu, Jia-He Yang, Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
Author contributions: Zhang Q and Yang JH provided the study concept and designed the research; Zhang Q, Li ZQ, Liu H and Yang JH performed the research; Zhang Q and Liu H provided the new reagents and analytical tools; Zhang Q and Yang JH analyzed and interpreted the data; Zhang Q, Li ZQ and Liu H wrote the paper; Zhang Q and Yang JH drafted the manuscript.
Supported by The National Natural Science Foundation of China, No. 30872998
Correspondence to: Jia-He Yang, MD, Professor, Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China. ehbhjhyang@163.com
Telephone: +86-21-81875262 Fax: +86-21-81875262
Received: April 19, 2011
Revised: June 16, 2011
Accepted: June 23, 2011
Published online: January 28, 2012
Abstract

AIM: To investigate the inhibitory effect of hepatitis B virus (HBV) preS2 antibody (preS2Ab) against HBV infection and HBV-associated hepatic carcinogenesis.

METHODS: An adenoviral vector carrying the full-length light and heavy chains of the HBV preS2Ab gene, Ad315-preS2Ab, was constructed. Enzyme linked immunosorbent assay (ELISA) and Western blotting analyses were used to determine the preS2Ab expression levels in vitro. Immunofluorescent techniques were used to examine the binding affinity between the expressed HBV preS2Ab and HBV-positive liver cells. ELISAs were also used to determine hepatitis B surface antigen (HBsAg) levels to assess the inhibitory effect of the preS2Ab against HBV infection in L02 cells. The inhibitory effect of preS2Ab against hepatic carcinogenesis was studied with diethylnitrosamine (DEN)-induced hepatocellular carcinomas (HCCs) in HBV transgenic mice.

RESULTS: The expression of HBV preS2Ab increased with increases in the multiplicity of infection (MOI) of Ad315-preS2Ab in L02 cells, with 350.87 ± 17.37 μg/L of preS2Ab when the MOI was 100 plaque forming units (pfu)/cell. The expressed preS2Abs could recognize liver cells from HBV transgenic mice. ELISA results showed that L02 cells expressing preS2Ab produced less HBsAg after treatment with the serum of HBV patients than parental L02 cells expressing no preS2Ab. HBV transgenic mice treated with Ad315-preS2Ab had fewer and smaller cancerous nodes after induction with DEN than mice treated with a blank Ad315 vector or untreated mice. Additionally, the administration of Ad315-preS2Ab could alleviate hepatic cirrhosis and decrease the serum levels of alanine transaminase and aspartate transaminase.

CONCLUSION: Adenovirus-mediated HBV preS2Ab expression could inhibit HBV infection in L02 cells, and then inhibit DEN-induced hepatocellular carcinogenesis and protect hepatic function in HBV transgenic mice.

Keywords: Hepatitis B virus; Adenoviral vector; PreS2 antibody; Hepatocellular carcinoma; Gene therapy