1. Immunization with HBsAg-Fc fusion protein induces a predominant production of Th1 cytokines and reduces HBsAg level in transgenic mice.
- Author
-
Meng ZF, Wang HJ, Yao X, Wang XY, Wen YM, Dai JX, Xie YH, and Xu JQ
- Subjects
- Animals, Chemokine CCL2 metabolism, Enzyme-Linked Immunosorbent Assay, Female, Hepatitis B Surface Antigens genetics, Immunity, Cellular immunology, Immunity, Humoral immunology, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Receptors, Fc genetics, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism, Tumor Necrosis Factor-alpha metabolism, Cytokines metabolism, Hepatitis B Surface Antigens immunology, Hepatitis B Surface Antigens metabolism, Receptors, Fc immunology, Receptors, Fc metabolism, Recombinant Fusion Proteins immunology
- 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., Conclusion: 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.
- Published
- 2012