A mouse model for HBV immunotolerance and immunotherapy

Dan Yang, Longchao Liu, Danming Zhu, Hua Peng, Lishan Su, Yang Xin Fu, Liguo Zhang

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Lack of an appropriate small animal model remains a major hurdle for studying the immunotolerance and immunopathogenesis induced by hepatitis B virus (HBV) infection. In this study, we report a mouse model with sustained HBV viremia after infection with a recombinant adeno-associated virus (AAV) carrying a replicable HBV genome (AAV/HBV). Similar to the clinical HBV carriers, the mice infected with AAV/HBV were sero-negative for antibodies against HBV surface antigen (HBsAg). Immunization with the conventional HBV vaccine in the presence of aluminum adjuvant failed to elicit an immune response against HBV in these mice. To identify a vaccine that can potentially circumvent this tolerance, the TLR9 agonist CpG was added to HBsAg as an adjuvant. Vaccination of mice with HBsAg/CpG induced not only clearance of viremia, but also strong antibody production and T-cell responses. Furthermore, both the DNA replication and protein expression of HBV were significantly reduced in the livers of AAV/HBV-infected mice. Accordingly, AAV/HBV-infected mice may be used as a robust model for investigating the underlying mechanism(s) of HBV immunotolerance and for developing novel immunotherapies to eradicate HBV infections.

Original languageEnglish (US)
Pages (from-to)71-78
Number of pages8
JournalCellular and Molecular Immunology
Volume11
Issue number1
DOIs
StatePublished - Jan 13 2014

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Keywords

  • AAV vector
  • HBV
  • Immunotherapy
  • Immunotolerance
  • Mouse model

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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