DefinePK

Abstract

The pathogen of hepatitis B (HBV), leading to liver cirrhosis and hepatocellular carcinoma, is the chronic carrier of more than 250 million individuals. HBV remains a significant global health problem. The highly immunogenic HBcAg nucleocapsid protein is both an immunological deception and a possible vaccine. This article examines the mechanisms by which HBcAg aids in immune evasion via T-cell exhaustion, Treg induction regulation, innate immune suppression, epigenetic changes, and APC impairment. These processes facilitate persistence of HBV through chronic infection. Nevertheless, due to its high immunogenicity and VLP structure, HBcAg is most suitable for therapeutic vaccines. Along with case histories pointing to clinical progress, innovative approaches like combination therapy, nanoparticle drug delivery, and mRNA vaccines are discussed. Pre-existing immunity, immune tolerance to stimuli, and genotypic heterogeneity are some of the issues that are targeted with an emphasis on cutting-edge therapies like immune checkpoint inhibitors and CRISPR-based therapies. The promise of HBcAg in eliciting functional cures of chronic HBV is emphasized in this review by integrating current studies, as well as future perspectives on personalized vaccines and novel delivery strategies to promote sustained viral clearance.