Strategies to Eliminate HBV Infection

Abstract

Chronic HBV infection is a major public health concern affecting over 240 million people worldwide. Although suppression of HBV replication is achieved in the majority of patients with currently available newer antivirals, discontinuation of therapy prior to hepatitis B surface antigen loss or seroconversion is associated with relapse of HBV in the majority of cases. Thus, new therapeutic modalities are needed to achieve eradication of the virus from chronically infected patients in the absence of therapy. The basis of HBV persistence includes viral and host factors. Here, we review novel strategies to achieve sustained cure or elimination of HBV. The novel approaches include targeting the viral and or host factors required for viral persistence, and novel immune-based therapies, including therapeutic vaccines.

Therapeutic cancer vaccines

“…These vaccine platforms include recombinant HBV proteins, DNA vaccines, recombinant virus vaccines, and subviral particles, as well as immune complexes of HBV surface antigen (HBsAg) and IgG anti-HBsAg (reviewed in ref. 61). Immune complex targeting through Fc receptors facilitates both DC ingestion of antigen and DC activation.…”

Synthetic RNAi triggers and their use in chronic hepatitis B therapies with curative intent

“…As discussed in other papers in this special issue, other novel approaches to CHB treatment are also being investigated (Kapoor and Kottilil, 2014). Therapies aimed at activating the innate immune system and restoring adaptive immune responses, including TLR agonists, PD-1 inhibitors, and therapeutic vaccines, would be particularly well suited to act synergistically with therapies such as RNAi aimed at reduction of viral antigens.…”

2′‐Fluoro‐6′‐methylene carbocyclic adenosine and its phosphoramidate prodrug: A novel anti‐HBV agent, active against drug‐resistant HBV mutants

“…Recent drug discovery efforts by biotech firms include (a) direct inhibition of viral replication using entry inhibitors; (b) targeting cccDNA; (c) inhibitors of nucleocapsid assembly (e.g., inhibition of capsid formation); (d) siRNA targeting viral transcription; (e) approaches to target the secretion of viral envelope proteins; (f) restoration of immune responses; (g) RNase H inhibitors . Most of these approaches are in different preclinical and clinical stages (Figure ) .…”