慢性乙型肝炎病毒感染（CHB）仍然是全球健康问题，目前可用的抗病毒疗法在预防肝细胞癌（HCC）发展方面效果有限。 CHB 治疗中的两个主要挑战包括乙型肝炎病毒 (HBV) 微型染色体、共价闭合环状 DNA (cccDNA) 的持续存在，以及宿主免疫反应未能消除 cccDNA。最近的研究结果表明，一些宿主和 HBV 蛋白参与 cccDNA 的表观遗传调控，包括 HBV 核心蛋白 (HBc) 和 HBV x 蛋白 (HBx)。这两种蛋白都可能有助于 cccDNA 微型染色体的稳定性，并与病毒和宿主蛋白相互作用以支持转录。慢性乙型肝炎治疗的一种潜在途径是使用治疗性疫苗。本文探索了适合 cccDNA 表观遗传学操作的 HBV 抗原，阐明了它们的作用机制，并评估了它们作为表观遗传学驱动的 CHB 治疗疫苗关键成分的潜力。分子靶向药物与治疗性疫苗相结合，通过靶向病毒并增强宿主的免疫反应，为解决慢性乙型肝炎提供了一种有前景的策略。尽管面临挑战，这些疫苗的开发强调需要能够诱导有效免疫反应而不导致 T 细胞耗竭的 HBV 抗原，为慢性乙型肝炎患者带来了新的希望。版权所有 © 2024。由 Elsevier España, S.L.U. 出版。

Chronic hepatitis B virus infection (CHB) remains a global health concern, with currently available antiviral therapies demonstrating limited effectiveness in preventing hepatocellular carcinoma (HCC) development. Two primary challenges in CHB treatment include the persistence of the minichromosome, covalently closed circular DNA (cccDNA) of the hepatitis B virus (HBV), and the failure of the host immune response to eliminate cccDNA. Recent findings indicate several host and HBV proteins involved in the epigenetic regulation of cccDNA, including HBV core protein (HBc) and HBV x protein (HBx). Both proteins might contribute to the stability of the cccDNA minichromosome and interact with viral and host proteins to support transcription. One potential avenue for CHB treatment involves the utilization of therapeutic vaccines. This paper explores HBV antigens suitable for epigenetic manipulation of cccDNA, elucidates their mechanisms of action, and evaluates their potential as key components of epigenetically-driven vaccines for CHB therapy. Molecular targeted agents with therapeutic vaccines offer a promising strategy for addressing CHB by targeting the virus and enhancing the host's immunological response. Despite challenges, the development of these vaccines provides new hope for CHB patients by emphasizing the need for HBV antigens that induce effective immune responses without causing T cell exhaustion.Copyright © 2024. Published by Elsevier España, S.L.U.