Poly I:C-based rHBVvac therapeutic vaccine eliminates HBV via generation of HBV-specific CD8+ effector memory T cells. Issue 11 (11th January 2019)

• Record Type: Journal Article
• Authors: Zhao, Hua-Jun; Han, Qiu-Ju; Wang, Guan; Lin, Ang; Xu, Dong-Qing; Wang, Ya-Qun; Zhao, Lian-Hui; Tian, Zhi-Gang; Zhang, Jian
• Is Part Of: Gut. Volume 68:Issue 11(2019)
• Page Start: 2032
• Page End: 2043
• Publication Date: 2019-01-11
• Subjects: hepatitis B -- immunology in hepatology -- adjuvant treatment -- T lymphocytes -- antiviral therapy; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2017-315588
• Languages: English
• ISSNs: 0017-5749

Abstract

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 CD11a hi CD8α lo cells. Importantly, we observed that T cell activation molecule KLRG1 was only expressed on HBV specific CD11a hi CD8α lo 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.