合成免疫策略治疗慢性乙肝病毒感染综述

Perspectives on Synthetic Immunity to Treat Chronic Hepatitis B Virus Infection

慢性乙型肝炎病毒(Hepatitis B Virus,HBV)感染可诱发肝硬化与肝癌,是危害人类健康的重大疾病。基于对HBV感染持续不愈主要是机体免疫功能缺陷所致的认识,提出用"合成免疫"策略重建抗HBV免疫功能,消除感染以预防致命病变的发生。用优化的基因治疗载体微环DNA,在体内表达一套工程抗体,模拟急性HBV感染康复时机体的免疫反应,由单克隆抗体中和病毒,双靶向抗体将非特异的T淋巴细胞转化为抗HBV的T淋巴细胞,杀死HBV感染的肝细胞,两者协同达到根治慢性HBV感染的目的。微环DNA安全、经济,可建立一个安全、高效、可负担的抗HBV免疫体系,有效消除HBV的危害。

Chronic infection of hepatitis B virus（HBV） is a severe public health problem because it affects millions of people worldwide and results in 600 thousand deaths from liver cirrhosis and hepatocarcinoma each year. Currently, no treatment is available to cure this disease. Here, we propose a synthetic immunity strategy to treat this disease. Specifi cally, minicircle DNA, an optimized non-viral vector, is used to express a group of engineered antibodies, of which the monoclonal antibodies act to neutralize the virus, while the bispecific antibodies（Bs Abs） to render the resting T lymphocytes the function of anti-HBV CTLs to eliminate HBV-infected hepatocytes. The two classes of antibodies work in concert to cure the disease as the host immune system eliminates the virus during recovering from acute infection. With the superior features in safety, transgene expression profi le and cost-effectiveness, minicircle can be used to establish a powerful anti-HBV synthetic immunity to achieve this goal.