**10. Concluding Remarks**

The development of preventative vaccines against hepatitis B resulted in remarkable advances in reducing HBV associated liver diseases. However, chronic hepatitis B is still difficult to control due to continuous viral replication driven by the episomal cccDNA present in the nuclei of infected hepatocytes. Novel strategies to generate vaccines based on structurally modified subunits to enhance immunogenicity and/or to modify antigen processing to change the hierarchy of epitope presentation may represent a pathway to overcome chronic viral infections or may complement a vaccine based on native proteins [65,218,224–226,231]. HBsAgS SVPs have been used as carrier platforms for various antigenic sequences to induce anti-foreign humoral and cellular immune responses [8,186]. One of the most advanced chimeric vaccines with a foreign antigenic sequence arrayed on a particulate carrier is based on the HBsAgS backbone fused to a *P. falciparum* CS-polypeptide [5,6]. For the design of next generation vaccines with therapeutic capabilities, formulations based on antigen combinations, such as mixtures of HBsAgS SVPs and SVPs composed of the HBV nucleocapsid antigen (HBcAg), may allow the induction of broad CD4 and CD8 T-cell responses suitable for therapeutic outcomes [232]. Alternatively, the assessment of synergistic effects between biochemically modified immunogens and adjuvant compounds possibly represent an avenue for the generation of optimized vaccines and delivery platforms, which may be suitable for therapeutic applications to overcome established chronic infections.

**Author Contributions:** H.-J.N. wrote the original draft version; J.K.-T.H. and B.J.-R. edited and reviewed the manuscript. All authors have read and agreed to the published version of the manuscript.

**Funding:** HJN was partly supported by a grant awarded by the Australian Centre for HIV and Viral Hepatitis Research (ACH2).

**Conflicts of Interest:** The author H.-J.N. of this publication has an equity interest in, and serves as a consultant to ClearB Therapeutics. ClearB Therapeutics had no role in the design and writing of the review article.
