Lu Mengji, Menne Stephan, Yang Dongliang, Xu Yang, Roggendorf Michael
Institut für Virologie, Universitätsklinikum Essen, Essen, Germany.
Expert Opin Investig Drugs. 2007 Jun;16(6):787-801. doi: 10.1517/13543784.16.6.787.
New therapeutic approaches for chronic hepatitis B virus infection based on immunomodulation are now under investigation. The woodchuck model for hepatitis B virus infection has emerged as a useful animal model for the evaluation of such approaches, after developing necessary assays and reagents for immunologic studies in this model. Conventional and novel vaccines such as DNA vaccines were tested in woodchucks for their ability to induce protective immune responses against challenge infection with the woodchuck hepatitis virus (WHV). Furthermore, immunotherapeutic approaches for the control of chronic hepadnaviral infection were evaluated in woodchucks. Immunizations with WHV proteins and DNA vaccines led to the development of antibodies to the WHV surface antigen and to a significant decrease of viral load in chronically WHV-infected woodchucks. Viral vector-mediated gene transfer was explored for the delivery of antiviral cytokines IFN-alpha in woodchucks and resulted in the decrease of viral replication. It is now generally accepted that a combination of antiviral treatment and immunization will be necessary to achieve successful immunomodulation with a long-term control of chronic hepatitis B virus infection.
基于免疫调节的慢性乙型肝炎病毒感染新治疗方法目前正在研究中。在开发出该模型免疫研究所需的检测方法和试剂后，土拨鼠乙型肝炎病毒感染模型已成为评估此类方法的有用动物模型。传统疫苗和新型疫苗（如DNA疫苗）在土拨鼠身上进行了测试，以评估它们诱导针对土拨鼠肝炎病毒（WHV）攻击感染的保护性免疫反应的能力。此外，还在土拨鼠身上评估了控制慢性嗜肝DNA病毒感染的免疫治疗方法。用WHV蛋白和DNA疫苗进行免疫接种导致慢性感染WHV的土拨鼠产生针对WHV表面抗原的抗体，并使病毒载量显著降低。探索了病毒载体介导的基因转移在土拨鼠体内递送抗病毒细胞因子IFN-α的作用，并导致病毒复制减少。现在人们普遍认为，抗病毒治疗和免疫接种相结合对于成功进行免疫调节以长期控制慢性乙型肝炎病毒感染是必要的。
