Guo Minggao, Kang Bin, Zheng Qi, Qian Qijun, Su Changqing, Wu Mengchao, Yang Jiamei
Department of Surgery, Shanghai Sixth Peoples Hospital, Shanghai Jiao Tong University, Shanghai 200233, China.
Acta Gastroenterol Belg. 2009 Jul-Sep;72(3):306-11.
Hepatitis B virus infection is a major problem in liver transplantation. In this study, we examined the potential efficay of a recombinant adenovirus expressing an antibody against the HBV preS2 antigen (Ab-H-HBV-S2) in preventing HBV recurrent infection after liver transplantation.
A gene for humanized antibody against the HBV preS2 antigen was cloned into pDC315, a type 5 adenoviral shuttle plasmid. Recombinant virus was obtained by homologous recombination in the 293 packaging cells. The virus containing the Ab-H-HBV-S2 gene was transduced into the rat liver graft during cold preservation. The recombinant virus produced antibody and showed protective effects on human hepatocytes from hepatitis B virus infection in vitro.
The recombinant virus titer determined by TCID50 analysis was 5.1x10(10) PFU/mL. The concentration of preS2 antibody in BALB/C nude mice was 16.7 +/- 10.5 microg/mL on day 3,30.9 +/- 13.6 pg/mL on day 7, and lasted for 5 weeks after the injection. At a concentration of 0.5 microg/mL or above, the preS2 antibody protected cultured human hepatocytes from hepatitis B virus.
Adenovirus-mediated gene transduction of anti-preS2 antibody in the transplanted liver may be a useful approach to prevent hepatitis B infection after liver transplantation.
乙型肝炎病毒感染是肝移植中的一个主要问题。在本研究中，我们检测了一种表达抗乙肝病毒前S2抗原抗体（Ab-H-HBV-S2）的重组腺病毒在预防肝移植后乙肝病毒复发感染方面的潜在疗效。
将抗乙肝病毒前S2抗原的人源化抗体基因克隆到5型腺病毒穿梭质粒pDC315中。通过在293包装细胞中的同源重组获得重组病毒。在冷保存期间，将含有Ab-H-HBV-S2基因的病毒转导至大鼠肝移植物中。该重组病毒产生抗体，并在体外对人肝细胞免受乙肝病毒感染显示出保护作用。
通过半数组织培养感染剂量（TCID50）分析测定的重组病毒滴度为5.1×10(10) PFU/mL。BALB/C裸鼠体内前S2抗体浓度在注射后第3天为16.7±10.5μg/mL，第7天为30.9±13.6μg/mL，并持续5周。在前S2抗体浓度为0.5μg/mL及以上时，可保护培养的人肝细胞免受乙肝病毒感染。
腺病毒介导的抗前S2抗体基因转导至移植肝脏中可能是预防肝移植后乙肝感染的一种有用方法。
