title: Immunization with HBsAg-Fc fusion protein induces a predominant production of Th1 cytokines and reduces HBsAg level in transgenic mice.
abstract: BACKGROUND
  The Fc receptor associated pathway might improve the immune responses against hepatitis B virus (HBV) as previously described by us. In addition, the Flt3 ligand (FL) has been reported to potentiate antigen presenting cells in vivo and may act as a potential adjuvant to boost antigen-specific immune responses. In this study, the immune efficacies of a set of fusion proteins of HBsAg and Fc and/or FL were evaluated in HBsAg transgenic mice.
  
  
  METHODS
  The fusion proteins composed of HBsAg and the Fc domain of murine IgG1 (HBsAg-Fc) and/or the Flt3 ligand, and yeast-derived recombinant HBsAg were used as immunogen to immunize HBsAg transgenic mice, respectively. Serum and liver HBsAg levels, serum anti-HBsAg and cytokine profile, and the activities of alanine aminotransferase (ALT)/AST were investigated after immunization.
  
  
  RESULTS
  After six injections, the most pronounced decrease in serum and liver HBsAg levels was observed in the HBsAg-Fc immunized group. In addition, serum Th1 cytokines and ALT/AST activities were highest in this group, indicating an effective induction of a favorable cellular immune response. Interestingly, the fusion protein containing HBsAg-Fc and the Flt3 ligand stimulated an alternative Th1-type immune response featured with high level productions of tumor necrosis factor α (TNF-α) and monocyte chemoabstractant protein 1 (MCP-1), causing a more severe cytotoxicity in hepatocytes while showed less effective in reducing serum HBsAg level.
  
  
  CONCLUSIONS
  HBsAg-Fc is effective in eliciting both the humoral and cellular immune responses against HBsAg in HBsAg transgenic mice, which makes it a potential immunogen for the immunotherapy of chronic hepatitis B.
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors.forename: Zhe-feng
authors.initials: ZF
authors.lastname: Meng
authors.forename: Hua-jing
authors.initials: HJ
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Yao
authors.forename: Xuan-yi
authors.initials: XY
authors.lastname: Wang
authors.forename: Yu-mei
authors.initials: YM
authors.lastname: Wen
authors.forename: Jian-xin
authors.initials: JX
authors.lastname: Dai
authors.forename: You-hua
authors.initials: YH
authors.lastname: Xie
authors.forename: Jian-qing
authors.initials: JQ
authors.lastname: Xu
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D007111:Immunity, Cellular / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D016207:Cytokines; D006514:Hepatitis B Surface Antigens; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha