Chronic hepatitis B is caused by prolonged infection with the hepatitis B virus (HBV), which can substantially increase the risk of developing liver disease. Despite the development of preventive vaccines against HBV, a therapeutic vaccine inducing an effective antibody response still remains elusive. The preS1 domain of the large HBV surface protein is the major viral attachment site on hepatocytes and thus offers a therapeutic target; however, its poor immunogenicity limits clinical translation. Here, we design a ferritin nanoparticle vaccine that can deliver preS1 to specific myeloid cells, including SIGNR1+ dendritic cells (which activate T follicular helper cells) and lymphatic sinus-associated SIGNR1+ macrophages (which can activate B cells). This nanoparticle vaccine induces a high-level and persistent anti-preS1 response that results in efficient viral clearance and partial serological conversion in a chronic HBV mouse model, offering a promising translatable vaccination strategy for the functional cure of chronic hepatitis B.

中文翻译：

---

双靶点纳米颗粒疫苗可引发针对慢性乙型肝炎的治疗性抗体反应。

慢性乙型肝炎是由乙型肝炎病毒（HBV）长期感染引起的，这会大大增加患肝病的风险。尽管针对乙型肝炎病毒的预防性疫苗已经开发出来，但诱导有效抗体反应的治疗性疫苗仍然难以捉摸。大 HBV 表面蛋白的 preS1 结构域是肝细胞上主要的病毒附着位点，因此提供了治疗靶点；然而，其较差的免疫原性限制了临床转化。在这里，我们设计了一种铁蛋白纳米颗粒疫苗，可以将 preS1 递送到特定的骨髓细胞，包括 SIGNR1+ 树突状细胞（可激活 T 滤泡辅助细胞）和淋巴窦相关的 SIGNR1+ 巨噬细胞（可激活 B 细胞）。