PT  - JOURNAL ARTICLE
AU  - Hua-Jun Zhao
AU  - Qiu-Ju Han
AU  - Guan Wang
AU  - Ang Lin
AU  - Dong-Qing Xu
AU  - Ya-Qun Wang
AU  - Lian-Hui Zhao
AU  - Zhi-Gang Tian
AU  - Jian Zhang
TI  - Poly I:C-based rHBVvac therapeutic vaccine eliminates HBV via generation of HBV-specific CD8<sup>+</sup> effector memory T cells
AID  - 10.1136/gutjnl-2017-315588
DP  - 2019 Nov 01
TA  - Gut
PG  - 2032--2043
VI  - 68
IP  - 11
4099  - http://gut.bmj.com/content/68/11/2032.short
4100  - http://gut.bmj.com/content/68/11/2032.full
SO  - Gut2019 Nov 01; 68
AB  - 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.