Chemical Design and Therapeutic Efficacy of Hbsag-Based Nanovaccines for Hepatitis B Virus Clearance: A Preclinical and Clinical Systematic Review Publisher



Marnani H N ; Mehrizi T Z ; Eshrati B ; Ardestani M S ; Ajdary N ; Vodjgani M ; Mosaffa N
Source: Advanced Pharmaceutical Bulletin Published:2026

Abstract

More than 240 million people worldwide are chronically infected with hepatitis B. Although current antiviral therapies effectively inhibit viral replication, they rarely result in a functional cure. The development of hepatitis B surface antigen (HBsAg)-based nanovaccines has emerged as a potential therapeutic strategy. The aim of this systematic review was to investigate a variety of formulations based on this system and determine their therapeutic efficacy in increasing antibody production, reducing HBsAg and hepatitis B virus DNA levels, stimulating T-cell responses, and reducing hepatitis B nuclear antigen (HBcAg)-positive hepatocytes. Studies published from 2015 to 2025 were included if they assessed the therapeutic benefits of HBsAg-based nanovaccines in animal models of chronic hepatitis B (CHB) or in human patients. A search of the PubMed/ Medline, Scopus, and Web of Science databases yielded 361 papers, of which eight, including seven preclinical trials and one clinical trial, satisfied the inclusion criteria. Both HBsAg-containing protein-based and mRNA-based nanovaccines demonstrated a significant ability to increase antibody production, reduce viral markers (HBsAg, HBV DNA, HBcAg, and cccDNA), and induce robust T-cell activation, while maintaining liver enzyme levels (ALT and AST) within the normal range. PreS1-targeting platforms (such as Ferritin NP-preS1) and mRNA-based lipid nanoparticles encoding HBsAg demonstrated enhanced therapeutic efficacy. The well-tolerated εPA-44 liposome vaccines, which were in phase II trials, demonstrated favorable clearance of HBV DNA. In conclusion, HBsAg-based nanovaccines show promising therapeutic potential for CHB by restoring antiviral immunity and reducing viral persistence. Large-scale clinical trials are necessary to confirm their efficacy and long-term safety. © 2026 The Author (s).