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cccDNA epigenetic regulator as target for therapeutical vaccine development against hepatitis B

Patricia Gita Naully1, Marselina Irasonia Tan2, Agustiningsih Agustiningsih3

  • 1School of Life Science and Technology, Institut Teknologi Bandung, Bandung 40132, Indonesia; Faculty of Health Sciences and Technology, Jenderal Achmad Yani University, Cimahi 40525, Indonesia.

Annals of Hepatology
|August 15, 2024
PubMed

Insights

New therapeutic vaccines targeting chronic hepatitis B virus (CHB) infection show promise. These vaccines aim to epigenetically modify hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and enhance immune response for better CHB treatment.

Area of Science:

  • Hepatology
  • Immunology
  • Virology

Background:

  • Chronic hepatitis B virus (CHB) infection is a global health issue with limited treatment efficacy against hepatocellular carcinoma (HCC).
  • Key challenges include the persistence of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and inadequate host immune response.
  • HBV core protein (HBc) and HBV x protein (HBx) are implicated in the epigenetic regulation and stability of cccDNA.

Purpose of the Study:

  • To explore HBV antigens for epigenetic manipulation of cccDNA in CHB therapy.
  • To elucidate the mechanisms of action of these antigens.
  • To evaluate their potential in epigenetically-driven therapeutic vaccines for CHB.

Main Methods:

  • Review of current literature on HBV antigens and epigenetic regulation of cccDNA.
  • Analysis of mechanisms by which HBc and HBx influence cccDNA stability and transcription.
  • Evaluation of therapeutic vaccine strategies involving HBV antigens for CHB treatment.

Main Results:

  • Identified potential HBV antigens suitable for epigenetic modification of cccDNA.
  • Elucidated mechanisms involving viral proteins (HBc, HBx) in cccDNA regulation.
  • Highlighted the role of molecular targeted agents combined with therapeutic vaccines.

Conclusions:

  • Epigenetic manipulation of cccDNA using targeted HBV antigens in therapeutic vaccines presents a promising strategy for CHB treatment.
  • This approach aims to overcome treatment limitations by enhancing host immunity and targeting viral persistence.
  • Further development is needed to identify antigens that elicit effective immune responses without causing T cell exhaustion.
Keywords:
chronic hepatitis Bcovalently closed circular DNAepigeneticimmune responsetherapeutic vaccine

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