Poly I:C-based rHBVvac therapeutic vaccine eliminates HBV via generation of HBV-specific CD8 + effector memory T cells

Hua Jun Zhao, Qiu Ju Han, Guan Wang, Ang Lin, Dong Qing Xu, Ya Qun Wang, Lian Hui Zhao, Zhi Gang Tian, Jian Zhang

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)2032-2043
Number of pages12
JournalGut
Volume68
Issue number11
DOIs
StatePublished - 2019
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology

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