Decoding HBV-specific adaptive immunity: from natural clearance to cure

Chronic HBV infection remains a major global health burden, with current antiviral therapies effectively suppressing viral replication but rarely achieving functional cure. Adaptive immunity is central to viral clearance but is profoundly impaired during chronic infection. Inducing and enhancing adaptive immunity through therapeutic vaccines, immune checkpoint inhibitors or T cell-based therapies represents a promising approach for HBV cure strategies. However, recent preclinical and clinical studies have demonstrated only limited efficacy, underscoring major immunological challenges. In this review, we summarise current knowledge of the correlates of viral clearance and persistence, discuss key unresolved questions and outline future research directions needed to advance immune-based HBV cure strategies.