title: Clearing Persistent Extracellular Antigen of Hepatitis B Virus: An Immunomodulatory Strategy To Reverse Tolerance for an Effective Therapeutic Vaccination.
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.
authors.affiliation: Institute of Biophysics-University of Texas Group for Immunotherapy, Chinese Academy of Sciences Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Chaoyang District, Beijing 100101, China;
authors.forename: Danming
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Institute of Biophysics-University of Texas Group for Immunotherapy, Chinese Academy of Sciences Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Chaoyang District, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China;
authors.forename: Longchao
authors.identifier: http://orcid.org/0000-0003-3394-5919
authors.initials: L
authors.lastname: Liu
authors.affiliation: Institute of Biophysics-University of Texas Group for Immunotherapy, Chinese Academy of Sciences Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Chaoyang District, Beijing 100101, China;
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Pathology and Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75225; and.
authors.forename: Sherry
authors.initials: S
authors.lastname: Fu
authors.affiliation: Institute of Biophysics-University of Texas Group for Immunotherapy, Chinese Academy of Sciences Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Chaoyang District, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China;
authors.forename: Yingjie
authors.identifier: http://orcid.org/0000-0002-9599-9907
authors.initials: Y
authors.lastname: Bian
authors.affiliation: Institute of Biophysics-University of Texas Group for Immunotherapy, Chinese Academy of Sciences Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Chaoyang District, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China;
authors.forename: Zhichen
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Institute of Biophysics-University of Texas Group for Immunotherapy, Chinese Academy of Sciences Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Chaoyang District, Beijing 100101, China;
authors.forename: Junming
authors.initials: J
authors.lastname: He
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Lishan
authors.identifier: http://orcid.org/0000-0002-0350-5560
authors.initials: L
authors.lastname: Su
authors.affiliation: Institute of Biophysics-University of Texas Group for Immunotherapy, Chinese Academy of Sciences Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Chaoyang District, Beijing 100101, China;
authors.forename: Liguo
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Biophysics-University of Texas Group for Immunotherapy, Chinese Academy of Sciences Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Chaoyang District, Beijing 100101, China; hpeng@moon.ibp.ac.cn Yang-Xin.Fu@UTSouthwestern.edu.
authors.forename: Hua
authors.initials: H
authors.lastname: Peng
authors.affiliation: Institute of Biophysics-University of Texas Group for Immunotherapy, Chinese Academy of Sciences Key Laboratory for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Chaoyang District, Beijing 100101, China; Department of Pathology and Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75225; and hpeng@moon.ibp.ac.cn Yang-Xin.Fu@UTSouthwestern.edu.
authors.forename: Yang-Xin
authors.initials: YX
authors.lastname: Fu
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002353:Carrier State; D004195:Disease Models, Animal; D005110:Extracellular Space; D006509:Hepatitis B / Q000276:immunology* / Q000517:prevention & control / Q000821:virology*; D006510:Hepatitis B Antibodies / Q000097:blood / Q000276:immunology; D006511:Hepatitis B Antigens / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D007108:Immune Tolerance; D056724:Immunity, Humoral; D056747:Immunomodulation; D051379:Mice; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014611:Vaccination
chemical_list: D057134:Antibodies, Neutralizing; D006510:Hepatitis B Antibodies; D006511:Hepatitis B Antigens; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D009838:Oligodeoxyribonucleotides