Nature Nanotechnology, 2 March, 2020，DOI：https://doi.org/10.1038/s41565-020-0648-y
Dual-targeting nanoparticle vaccine elicits a therapeutic antibody response against chronic hepatitis B
Wenjun Wang, Xiaoxiao Zhou, Yingjie Bian, Shan Wang, Qian Chai, Zhenqian Guo, Zhenni Wang, Ping Zhu, Hua Peng, Xiyun Yan, Wenhui Li, Yang-Xin Fu & Mingzhao Zhu
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.