Int J Biol Sci 2022; 18(1):154-165. doi:10.7150/ijbs.62424 This issue

Research Paper

CpG-C ODN M362 as an immunoadjuvant for HBV therapeutic vaccine reverses the systemic tolerance against HBV

Huajun Zhao, Qiuju Han, Ailu Yang, Yucan Wang, Guan Wang, Ang Lin, Xiao Wang, Chunlai Yin, Jian Zhang

Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, Jinan, China.

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Zhao H, Han Q, Yang A, Wang Y, Wang G, Lin A, Wang X, Yin C, Zhang J. CpG-C ODN M362 as an immunoadjuvant for HBV therapeutic vaccine reverses the systemic tolerance against HBV. Int J Biol Sci 2022; 18(1):154-165. doi:10.7150/ijbs.62424. Available from

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Graphic abstract

Chronic Hepatitis B virus (CHB) infection is a global public health problem. Oligodeoxynucleotides (ODNs) containing class C unmethylated cytosine-guanine dinucleotide (CpG-C) motifs may provide potential adjuvants for the immunotherapeutic strategy against CHB, since CpG-C ODNs stimulate both B cell and dendritic cell (DC) activation. However, the efficacy of CpG-C ODN as an anti-HBV vaccine adjuvant remains unclear. In this study, we demonstrated that CpG M362 (CpG-C ODN) as an adjuvant in anti-HBV vaccine (cHBV-vaccine) successfully and safely eliminated the virus in HBV-carrier mice. The cHBV-vaccine enhanced DC maturation both in vivo and in vitro, overcame immune tolerance, and recovered exhausted T cells in HBV-carrier mice. Furthermore, the cHBV-vaccine elicited robust hepatic HBV-specific CD8+ and CD4+ T cell responses, with increased cellular proliferation and IFN-γ secretion. Additionally, the cHBV-vaccine invoked a long-lasting follicular CXCR5+ CD8+ T cell response following HBV re-challenge. Taken together, CpG M362 in combination with rHBVvac cleared persistent HBV and achieved long-term virological control, making it a promising candidate for treating CHB.

Keywords: chronic hepatitis B, CpG-C ODN, therapeutic vaccine, adjuvant, immune-tolerance, CXCR5+ CD8+ T cells