New ideas, challenges and strategies about research on hepatitis C vaccine
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摘要:
丙型肝炎病毒(HCV)感染是引起慢性肝病的主要原因之一,严重危害人类健康,目前抗病毒治疗的标准方案为聚乙二醇干扰素α(PEG-IFN-α)联合利巴韦林,其有效率仅为50%70%,且疫苗研究进展缓慢,已成为严峻的公共卫生问题。近10多年来,对HCV感染发病机制、保护性免疫应答和病毒持续感染机制的认识取得了很大进展,中和抗体以及CD4+和CD8+T细胞在内的强烈的T细胞免疫应答已被证明与HCV的清除相关,这将是研制丙型肝炎疫苗的希望所在。当前HCV疫苗的研究主要集中在多肽疫苗、核酸疫苗、病毒载体疫苗、重组多表位疫苗、以抗原递呈细胞为载体的树突状细胞(DC)疫苗等,已有多种疫苗正在研制并进行进入临床试验前的测试。我们结合多年来对HCV的研究基础,通过与国内外同行交流,提出变"单纯预防"为"防治结合,以诱导持续免疫应答和维持病毒抑制状态为基本目标"的HCV疫苗研究新理念,发展以诱导细胞免疫为主的预防和治疗性疫苗,尤其是既能在体内有效激发HCV特异性细胞毒性T淋巴细胞(CTL)反应,又能维持CD4+记忆T细胞功能的治疗性细胞疫苗。本文综述关于HCV保护性免疫应答及持续感染的...
Abstract:Hepatitis C virus (HCV) is a major public health problem and a leading cause of chronic liver disease.Unfortunately, there is no vaccine against HCV and the current standard anti-viral therapy is the combination of pegylated IFN-α with ribavirin, which is only effective in 50%-70% of the patients with HCV infection.Great strides have been made over the past decades, and much has been learned about the pathogenesis of hepatitis C, protective immunity against HCV and causes of persistent infection.Neutralizing antibodies and robust T cell responses including both CD4+ and CD8+ have been shown to be related to the clearance of HCV, which have shed lights on the potential success of HCV vaccines.Recently, there are many HCV vaccines under development, including multi-peptides vaccines, DNA vaccines, recombinant multi-epitopes vaccines, dendritic cell vaccines, etc and many of which were tested before entering into clinical trials.After years of HCV research, it is suggested that we should change our ideas in HCV vaccine research from simply prevention to the cooperation of prevention and treatment, which could induce the persistent immune response and virus inhibition.In this review, we discuss the protective host immunity against HCV and the mechanisms of persistent HCV infection, the challenges, new ideas and strategies in HCV vaccine research are also included.
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Key words:
- hepatitis C /
- viral hepatitis vaccines
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