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

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

    Hua-Jun Zhao1, Qiu-Ju Han1, Guan Wang1, Ang Lin1, Dong-Qing Xu1, Ya-Qun Wang1, Lian-Hui Zhao1, Zhi-Gang Tian2, Jian Zhang1

Author affiliations

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

    Correspondence to Dr Jian Zhang, Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, Shandong, 250012, China; [email protected]

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.
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http://dx.doi.org/10.1136/gutjnl-2017-315588

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Footnotes

    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) .