Dual-targeting nanoparticle vaccine elicits a therapeutic antibody response against chronic hepatitis B.

Abstract

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.

• Authors: 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
• Journal: Nature nanotechnology (Nat Nanotechnol) Vol. 15 Issue 5 Pg. 406-416 (05 2020) ISSN: 1748-3395 [Electronic] England
• PMID: 32123380 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hepatitis B Surface Antigens
• Hepatitis B Vaccines
• Protein Precursors
• presurface protein 1, hepatitis B surface antigen

Topics

• Animals
• Antibody Formation
• Female
• Hepatitis B Surface Antigens (administration & dosage, therapeutic use)
• Hepatitis B Vaccines (administration & dosage, therapeutic use)
• Hepatitis B virus (immunology)
• Hepatitis B, Chronic (immunology, prevention & control)
• Male
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Myeloid Cells (immunology)
• Nanoparticles (administration & dosage, therapeutic use)
• Protein Precursors (administration & dosage, therapeutic use)