Therapeutic vaccines in HBV: lessons from HCV

战天斗hbv

Currently, millions of people infected with hepatitis B virus (HBV) are committed to decades of treatment with anti-viral therapy to control viral replication. However, new tools for immunotherapy that include both viral vectors and molecular checkpoint inhibitors are now available. This has led to a resurgence of interest in new strategies to develop immunotherapeutic strategies with the aim of inducing HBeAg seroconversion—an end-point that has been associated with a decrease in the rates of disease progression. Ultimately, a true cure will involve the elimination of covalently closed circular DNA which presents a greater challenge for immunotherapy. In this manuscript, I describe the development of immunotherapeutic strategies for HBV that are approaching or currently in clinical studies, and draw on observations of T cell function in natural infection supported by recent animal studies that may lead to additional rational vaccine strategies using checkpoint inhibitors. I also draw on our recent experience in developing potent vaccines for HCV prophylaxis based on simian adenoviral and MVA vectors used in prime–boost strategies in both healthy volunteers and HCV infected patients. I have shown that the induction of T cell immune responses is markedly attenuated when administered to people with persistent HCV viremia. These studies and recently published animal studies using the woodchuck model suggest that potent vaccines based on DNA or adenoviral vectored vaccination represent a rational way forward. However, combining these with drugs to suppress viral replication, alongside checkpoint inhibitors may be required to induce long-term immune control.

战天斗hbv

目前，数以百万计的人感染乙型肝炎病毒（HBV）致力于数十年的治疗与抗病毒治疗来控制病毒复制。然而，现在可用于免疫治疗的新工具，包括病毒载体和分子检查点抑制剂。这导致了在新的战略兴趣的复苏发展与诱导HBeAg血清学转换，一个已经在疾病进展的速度下降有关终点的目的免疫治疗策略。最终，真正的治愈将涉及消除共价闭合环状DNA它提​​出了免疫更大的挑战。在这份手稿，我描述的免疫治疗策略的发展HBV那些在临床研究中接近或当前和借鉴T细胞功能最近的动物研究支持自然感染的意见，可能会导致使用检查点抑制剂额外理性疫苗策略。我还利用我们最近在开发有效的疫苗的基础上在健康志愿者和HCV感染患者初免 - 加强策略用猿猴腺病毒和MVA载体HCV预防经验。我已经表明，T细胞的免疫应答的诱导当给予患有持久性的HCV病毒血症显着衰减。这些研究和使用土拨鼠模型最近发表的动物研究表明，基于DNA或腺病毒接种向量强有力的疫苗代表了一种理性的方式。然而，用药物组合这些来抑制病毒的复制，沿着检查点抑制剂，可能需要以诱导长期免疫控制

战天斗hbv

These studies and recently published animal studies using the woodchuck model suggest that potent vaccines based on DNA or adenoviral vectored vaccination represent a rational way forward

没有好的模型、