Roggendorf M, Yang D, Lu M
Institute for Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
Pathol Biol (Paris). 2010 Aug;58(4):308-14. doi: 10.1016/j.patbio.2010.04.005. Epub 2010 Jun 19.
Interferon-alpha and nucleoside analogues are available for the treatment of chronic hepatitis B virus (HBV) infection but do not lead to a satisfactory result. New findings about the immunological control of HBV during acute infection suggest the pivotal role of T-cell mediated immune responses. Several preclinical and clinical trials were undertaken to explore the possibility of stimulating specific immune responses in chronically infected animals and patients by vaccination. However, vaccination with commercially available HBV vaccines in patients and immunization in woodchucks with core or surface proteins of woodchuck hepatitis virus (WHV) did not result in effective control of HBV and WHV infection, suggesting that new formulations of therapeutic vaccines are needed. Some new approaches combining antiviral treatments with nucleoside analogues, DNA vaccines and protein vaccines were tested in the woodchuck model. It could be shown that therapeutic vaccinations are able to stimulate specific B- and T-cell responses and to achieve transient suppression of viral replication. These results suggest the great potential of therapeutic vaccination in combination with antivirals to reach an effective and sustained control of HBV infection.
干扰素-α和核苷类似物可用于治疗慢性乙型肝炎病毒（HBV）感染，但效果并不理想。关于急性感染期间HBV免疫控制的新发现表明T细胞介导的免疫反应起关键作用。开展了多项临床前和临床试验，以探索通过接种疫苗刺激慢性感染动物和患者特异性免疫反应的可能性。然而，在患者中接种市售HBV疫苗以及在土拨鼠中用土拨鼠肝炎病毒（WHV）的核心或表面蛋白进行免疫接种，均未有效控制HBV和WHV感染，这表明需要新的治疗性疫苗配方。在土拨鼠模型中测试了一些将抗病毒治疗与核苷类似物、DNA疫苗和蛋白质疫苗相结合的新方法。结果表明，治疗性疫苗接种能够刺激特异性B细胞和T细胞反应，并实现病毒复制的短暂抑制。这些结果表明，治疗性疫苗与抗病毒药物联合使用在有效且持续控制HBV感染方面具有巨大潜力。
