Hepatitis B core antigen-human invariant chain fusion protein (HBc-Ii)

The Hepatitis B core antigen-human invariant chain fusion protein is a therapeutic vaccine construct designed to enhance the immune response against chronic Hepatitis B virus (HBV) infection [1]. This chimeric molecule consists of the Hepatitis B core antigen (HBc) fused to the human invariant chain (Ii, also known as CD74), a chaperone protein that naturally directs MHC class II molecules to the endosomal/lysosomal compartments for peptide loading [2]. By leveraging the trafficking signals of the invariant chain, the HBc antigen is efficiently routed into the MHC class II presentation pathway, which significantly boosts the activation and proliferation of CD4+ helper T cells [3]. This strategy aims to overcome the immune tolerance and T-cell exhaustion typically observed in chronic HBV patients, providing the necessary T-cell help to stimulate B-cell antibody production and support CD8+ cytotoxic T-lymphocyte activity [4]. Clinical candidates such as JNJ-64300535 utilize this fusion technology within DNA or viral vector platforms to induce a robust, multi-specific immune response [5]. The primary therapeutic goal is to achieve functional cure, characterized by the sustained loss of Hepatitis B surface antigen (HBsAg) and undetectable HBV DNA [1]. While the construct itself is highly immunogenic, safety monitoring is critical, particularly regarding liver enzyme flares (ALT/AST) that may occur as the immune system begins to clear infected hepatocytes [4]. Sources: [1] Janssen Research & Development (2018) ClinicalTrials.gov NCT03463369; [2] Roche & Furuta (2015) Nat Rev Immunol 15(4):203-216; [3] Diebold et al. (2001) Gene Ther 8(6):487-493; [4] Zoulim et al. (2016) Antiviral Res 133:136-148; [5] Janssen (2020) J Hepatol 73:S53-S54.

Other names

HBc-CD74 fusionIi-HBc fusionMHC II-targeted HBc antigenCD74-HBc chimeric proteinHepatitis B core antigen-CD74 fusion

Enhancement of MHC class II antigen presentation by directing the HBc antigen to the endosomal/lysosomal compartment via the invariant chain (CD74) trafficking signals.