Clearing persistent extracellular antigen of hepatitis B virus: An immunomodulatory strategy to reverse tolerance for an effective therapeutic vaccination

Danming Zhu, Longchao Liu, Dan Yang, Sherry Fu, Yingjie Bian, Zhichen Sun, Junming He, Lishan Su, Liguo Zhang, Hua Peng, Yang Xin Fu

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Development of therapeutic vaccines/strategies to control chronic hepatitis B virus (HBV) infection has been challenging because of HBV-induced tolerance. In this study, we explored strategies for breaking tolerance and restoring the immune response to the HBV surface Ag in tolerant mice. We demonstrated that immune tolerance status is attributed to the level and duration of circulating HBsAg in HBV carrier models. Removal of circulating HBsAg by a monoclonal anti-HBsAg Ab in tolerant mice could gradually reduce tolerance and reestablish B cell and CD4+ T cell responses to subsequent Engerix-B vaccination, producing protective IgG. Furthermore, HBsAg-specific CD8+ T cells induced by the addition of a TLR agonist resulted in clearance of HBV in both serum and liver. Thus, generation of protective immunity can be achieved by clearing extracellular viral Ag with neutralizing Abs followed by vaccination.

Original languageEnglish (US)
Pages (from-to)3079-3087
Number of pages9
JournalJournal of Immunology
Volume196
Issue number7
DOIs
StatePublished - Apr 1 2016

ASJC Scopus subject areas

  • Immunology

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