Poly I：基于C的rHBVvac治疗性疫苗通过产生HBV特异性CD8 +效应记

StephenW

Gut. 2019 Jan 11. pii: gutjnl-2017-315588. doi: 10.1136/gutjnl-2017-315588. [Epub ahead of print]
Poly I:C-based rHBVvac therapeutic vaccine eliminates HBV via generation of HBV-specific CD8+ effector memory T cells.
Zhao HJ1, Han QJ1, Wang G1, Lin A1, Xu DQ1, Wang YQ1, Zhao LH1, Tian ZG2, Zhang J1.
Author information

1
    Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, Jinan, China.
2
    School of Life Sciences, University of Science and Technology of China, Hefei, China.

Abstract
OBJECTIVE:

Chronic hepatitis B (CHB) virus infection is a global health problem. Finding a cure for CHB remains a challenging task.
DESIGN:

In this study, poly I:C was employed as an adjuvant for HBV therapeutic vaccine (referred to as pHBV-vaccine) and the feasibility and efficiency of pHBV-vaccine in CHB treatment were evaluated in HBV-carrier mice.
RESULTS:

We found that pHBV-vaccine decreased HBsAg and HBV DNA efficiently and safely in HBV-carrier mice. Further investigation showed that pHBV-vaccine promoted maturation and antigen presentation ability of dendritic cells in vivo and in vitro. This vaccine successfully restored the exhaustion of antigen-specific CD8+ T cells and partly broke the immune tolerance established in HBV-carrier mice. pHBV-vaccine also enhanced the proliferation and polyfunctionality of HBV-specific CD11ahi CD8αlo cells. Importantly, we observed that T cell activation molecule KLRG1 was only expressed on HBV specific CD11ahi CD8αlo cells. Furthermore, pHBV-vaccine reduced the expression of Eomes and increased the serum IL-12 levels, which in turn promoted the generation of effector memory short-lived effector cells (SLECs) to exhibit a critical role in HBV clearance. SLECs induced by pHBV-vaccine might play a crucial role in protecting from HBV reinfection.
CONCLUSIONS:

Findings from this study provide a new basis for the development of therapeutic pHBV-vaccine, which might be a potential candidate for clinical CHB therapy.

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
KEYWORDS:

T lymphocytes; adjuvant treatment; antiviral therapy; hepatitis B; immunology in hepatology

PMID:
    30635406
DOI:
    10.1136/gutjnl-2017-315588

StephenW

肠道。 2019年1月11日.pii：gutjnl-2017-315588。 doi：10.1136 / gutjnl-2017-315588。 [提前打印]
Poly I：基于C的rHBVvac治疗性疫苗通过产生HBV特异性CD8 +效应记忆T细胞来消除HBV。
赵HJ1，韩QJ1，王G1，林A1，徐DQ1，王YQ1，赵丽麟，田志庚，张J1。
作者信息

1
    山东大学药学院免疫药物研究所，济南，中国。
2
    中国科学技术大学生命科学学院，中国合肥。

抽象
目的：

慢性乙型肝炎（CHB）病毒感染是一个全球性的健康问题。找到治疗CHB的方法仍然是一项具有挑战性的任务。
设计：

在该研究中，使用poly I：C作为HBV治疗性疫苗（称为pHBV-疫苗）的佐剂，并且在HBV-载体小鼠中评估pHBV-疫苗在CHB治疗中的可行性和效率。
结果：

我们发现pHBV疫苗在HBV携带者小鼠中有效且安全地降低了HBsAg和HBV DNA。进一步的研究表明，pHBV疫苗在体内和体外促进了树突状细胞的成熟和抗原呈递能力。该疫苗成功地恢复了抗原特异性CD8 + T细胞的耗尽，并部分破坏了HBV携带者小鼠中建立的免疫耐受性。 pHBV疫苗还增强了HBV特异性CD11ahiCD8αlo细胞的增殖和多功能性。重要的是，我们观察到T细胞活化分子KLRG1仅在HBV特异性CD11ahiCD8αlo细胞上表达。此外，pHBV疫苗降低了Eomes的表达并增加了血清IL-12水平，从而促进了效应记忆短寿命效应细胞（SLEC）的产生，从而在HBV清除中发挥关键作用。 pHBV疫苗诱导的SLEC可能在防止HBV再感染中起关键作用。
结论：

该研究的结果为开发治疗性pHBV疫苗提供了新的基础，该疫苗可能是临床CHB治疗的潜在候选者。

©作者（或其雇主）2019。无商业再利用。请参阅权限。由BMJ发布。
关键词：

T淋巴细胞;辅助治疗;抗病毒治疗;乙型肝炎;肝病学免疫学

结论：
    30635406
DOI：
    10.1136 / gutjnl-2017-315588