慢性乙型肝炎治疗性核酸和病毒载体疫苗的研究进展  

Research Progress of Therapeutic Nucleic Acid and Viral Vector Vaccines against Chronic Hepatitis B

作　　者：陈孟璋 林汉森 CHEN Meng-zhang;LIN Han-sen(Guangzhou Guangyao Yigan Biological Products Co.,Ltd,Guangzhou 511495,China)

机构地区：[1]广州广药益甘生物制品股份有限公司,广东广州511495

出　　处：《药物生物技术》2023年第1期83-89,共7页Pharmaceutical Biotechnology

基　　金：国家“艾滋病和病毒性肝炎等重大传染病防治”科技重大专项(No.2014ZX10002002);广州市健康医疗协同创新重大计划(No.201803040013)。

摘　　要：慢性乙型肝炎(Chronic Hepatitis B,CHB)是全球性的公共卫生问题,可能导致肝硬化,并极大地增加肝细胞癌发生的风险,严重危害人类健康。现有药物难以满足治疗需求,核苷(酸)类似物通常需要长期甚至终生服药,干扰素α副作用明显,因此迫切需要新的治疗药物。在急性乙型肝炎中,强烈的免疫反应对于清除病毒是必须的,而在慢性感染中只存在弱免疫反应。CHB患者的乙型肝炎病毒特异性细胞免疫状态是决定慢性感染临床转归的重要因素之一,提高特异性免疫应答水平是治疗CHB的关键。治疗性核酸和病毒载体疫苗含有经基因工程技术改造的、可编码病毒蛋白的DNA或RNA分子,接种后可内源性表达抗原,具有诱导或增强特异性免疫特别是细胞免疫的特点,有望成为CHB治疗的重要手段。国内外已研发了一系列CHB治疗性核酸和病毒载体疫苗,文章将对这些疫苗的研发进展进行综述和展望,以期为疫苗研发和CHB治疗提供参考。Chronic Hepatitis B(CHB)is a public health problem worldwide,which may lead to cirrhosis and greatly increase the risk of hepatocellular carcinoma,so that seriously affect human health.Current drugs cannot meet the demand for treatment.Longterm or even lifelong treatment is usually required for nucleos(t)ide analogues and significant side effects are observed with interferonalpha therapy.Therefore,new drugs are urgently needed for CHB treatment.In acute hepatitis B virus infection a strong immune response is necessary to clear the virus,but in chronic infection the immune response is weakened and dysfunctional.The state of Hepatitis B virus specific cellular immune response of CHB patients is considered to be one of the important factors that determine the clinical outcome of chronic infection.It is critical to improve the level of specific immune response for CHB treatment.Therapeutic nucleic acid and viral vector vaccines contain DNA or RNA molecules modified by genetic engineering technology that can encode viral proteins.Antigens are expressed endogenously after inoculation.These vaccines have been shown to induce or enhance antigenspecific immune responses,especially cellular immunity,and are expected to be an important strategy for the treatment of CHB.A series of therapeutic nucleic acid and viral vector vaccines against CHB have been developed.This article present a review and prospect on the study progress of these vaccines in order to provide reference for vaccine development and CHB treatment.

关 键 词：慢性乙型肝炎 治疗性疫苗 核酸疫苗 病毒载体疫苗 特异性免疫应答 HBV特异性细胞免疫 

分 类 号：R186[医药卫生—流行病学] R512.62[医药卫生—公共卫生与预防医学]