Therapeutic vaccines in HBV: lessons from HCV.
Therapeutic vaccines in HBV: lessons from HCV.
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DOI：
10.1007/s00430-014-0376-8
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发表时间：
2015-02
影响因子：
5.4
通讯作者：
Barnes E
中科院分区：
文献类型：
--
作者：
Barnes E
目前，数百万感染B型肝炎病毒（HBV）的人致力于数十年的抗病毒治疗以控制病毒复制。然而，包括病毒载体和分子检查点抑制剂的免疫治疗新工具现在已经可用。这导致了对新策略的兴趣的复苏，以开发免疫策略，目的是诱导HBeAg血清转化-一个与疾病进展率降低相关的终点。最终，真正的治愈将涉及消除共价闭合的环状DNA，这对免疫疗法提出了更大的挑战。在这篇手稿中，我描述了HBV免疫策略的发展，这些策略正在接近或目前正在临床研究中，并借鉴了最近动物研究支持的自然感染中T细胞功能的观察结果，这些研究可能会导致使用检查点抑制剂的其他合理疫苗策略。我还借鉴了我们最近的经验，在健康志愿者和HCV感染的患者中，基于猴腺病毒和MVA载体用于初免-加强策略，开发有效的HCV预防疫苗。我已经证明，当给予持续性HCV病毒血症患者时，T细胞免疫应答的诱导明显减弱。这些研究和最近发表的使用土拨鼠模型的动物研究表明，基于DNA或腺病毒载体接种的有效疫苗代表了一种合理的前进方向。然而，将这些药物与抑制病毒复制的药物结合，以及检查点抑制剂可能需要诱导长期的免疫控制。
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.
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