A CpG 1018S/QS-21-Adjuvanted HBsAg Therapeutic Vaccine as a Novel Strategy Against HBV

作者：Zixuan Wang, Jing Wu, Xiaohan Meng, He Zhang Weng, Qiang Li, Lin Li, Zhiyong Ma, Shengli Bi, Qiuju Han, Huajun Zhao, Cunbao Liu, Deping Meng · 发表于：Vaccines · 年份：2025 · DOI：10.3390/vaccines13101014 · 被引用次数：2 · 研究领域：Hepatitis B Virus Studies、Viral gastroenteritis research and epidemiology、Immunotherapy and Immune Responses

Chronic hepatitis B virus (HBV) infection remains a major global health challenge, substantially contributing to liver-related morbidity and mortality. Background/Objectives: Developing therapeutic strategies that overcome immune tolerance and achieve functional cures is an urgent priority. Methods: In this study, we report a therapeutic vaccine comprising hepatitis B surface antigen (HBsAg) formulated with the dual adjuvant system CpG 1018S and QS-21. The immunogenicity and therapeutic efficacy of this vaccine were systematically evaluated in an rAAV8-HBV1.3-established chronic HBV mouse model. Results: The vaccine elicited a robust Th1-skewed immune response, characterized by elevated anti-HBs IgG2b titers and an increased IgG2b/IgG1 ratio. Notably, immunized mice showed markedly reduced circulating HBsAg levels. Mechanistically, the CpG 1018S and QS-21 adjuvant system enhanced dendritic cell activation, maturation, and antigen presentation, expanded HBV-specific CD4+ and CD8+ T cell populations, and attenuated the expression of the exhaustion markers TIM-3 and TIGIT. Additionally, immunized mice exhibited restored T cell polyfunctionality, with an increased secretion of effector cytokines, including TNF-α and IL-21. These responses collectively contributed to the reversal of T cell exhaustion and breakdown of immune tolerance, facilitating sustained viral suppression. Conclusions: Our findings demonstrate that the CpG 1018S/QS-21-adjuvanted vaccine induces potent humoral a...