title: Immuno-potentiating pathway of HBsAg-HBIG immunogenic complex visualized.
abstract: Chronic viral hepatitis B (CHB) is a major global health problem. A therapeutic vaccine for CHB comprised of yeast-derived recombinant HBsAg-anti-HBs immunogenic complexes (YIC) has been devloped by us. A series of clinical trials has shown its therapeutic efficacy in decreasing HBV viral load and converting serum HBeAg-positive to anti-HBe-positive status in a subpopulation of CHB patients. Herein, we present a study of the immuno-potentiating mechanisms of YIC revealed by live-cell imaging technology. We studied internalization and dissociation of YIC in cells in vitro, and antigen presentation and T cell stimulation in mice. We found that after YIC was internalized via the Fcγ receptors (FcγR) of antigen presenting cells, it was subsequently transferred through early and late endosomal into lysosomal compartments. The dissociation of YIC was mainly observed in the late endosome. Furthermore when YIC were injected into mice, the populations of IFN-γ- and TNF-α-producing CD8+ and CD4+ T cells were higher in the YIC group than in controls receiving antigen or antibody alone. These observations supplement the known mechanisms of YIC action as a therapeutic vaccine for CHB.
authors.affiliation: a Key Laboratory of Medical Molecular Virology of MOH and MOE; Fudan University Shanghai Medical College ; Shanghai , China.|b China State Key Laboratory for Agro-Biotechnology; College of Biological Science; China Agricultural University ; Beijing , China.
authors.forename: Hu
authors.initials: H
authors.lastname: Liu
authors.affiliation: a Key Laboratory of Medical Molecular Virology of MOH and MOE; Fudan University Shanghai Medical College ; Shanghai , China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Geng
authors.affiliation: a Key Laboratory of Medical Molecular Virology of MOH and MOE; Fudan University Shanghai Medical College ; Shanghai , China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: b China State Key Laboratory for Agro-Biotechnology; College of Biological Science; China Agricultural University ; Beijing , China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wu
authors.affiliation: b China State Key Laboratory for Agro-Biotechnology; College of Biological Science; China Agricultural University ; Beijing , China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xie
authors.affiliation: b China State Key Laboratory for Agro-Biotechnology; College of Biological Science; China Agricultural University ; Beijing , China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.affiliation: a Key Laboratory of Medical Molecular Virology of MOH and MOE; Fudan University Shanghai Medical College ; Shanghai , China.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: a Key Laboratory of Medical Molecular Virology of MOH and MOE; Fudan University Shanghai Medical College ; Shanghai , China.
authors.forename: Xuanyi
authors.initials: X
authors.lastname: Wang
authors.affiliation: a Key Laboratory of Medical Molecular Virology of MOH and MOE; Fudan University Shanghai Medical College ; Shanghai , China.
authors.forename: Di
authors.initials: D
authors.lastname: Qu
authors.affiliation: a Key Laboratory of Medical Molecular Virology of MOH and MOE; Fudan University Shanghai Medical College ; Shanghai , China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Wen
authors.affiliation: a Key Laboratory of Medical Molecular Virology of MOH and MOE; Fudan University Shanghai Medical College ; Shanghai , China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology / Q000378:metabolism*; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004705:Endocytosis; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000276:immunology / Q000378:metabolism*; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D021381:Protein Transport
chemical_list: D000936:Antigen-Antibody Complex; D006514:Hepatitis B Surface Antigens; D007136:Immunoglobulins; C045213:hepatitis B hyperimmune globulin
keywords: HBsAg-anti-HBs complex; chronic hepatitis B; cross-presentation; dendritic cells; therapeutic vaccine