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.
- hepatitis B
- immunology in hepatology
- adjuvant treatment
- T lymphocytes
- antiviral therapy
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Contributors All authors listed have contributed to the work described in the article. Conceived and designed the experiments: JZ, ZT, HZ. Performed the experiments: HZ, GW, AL. Analysed the data: HZ, QH, DX, YW, LZ. Wrote the paper: HZ and JZ.
Funding This work was supported by grants from National Basic Research Program of China (No. 2013CB531503) and the National Major Science & Technology Project for Control and Prevention of Major Infectious Diseases in China (No. 2018ZX10301401) .
Competing interests None declared.
Patient consent Not required.
Ethics approval The Institutional Animal Care and Use Committee of the Shandong University.
Provenance and peer review Not commissioned; externally peer reviewed.