Details

Autor(en) / Beteiligte

• Meng, Zhe-feng
• Wang, Hua-jing
• Yao, Xin
• Wang, Xuan-yi
• Wen, Yu-mei
• Dai, Jian-xin
• Xie, You-hua
• Xu, Jian-qing

Titel

Immunization with HBsAg-Fc fusion protein induces a predominant production of Th1 cytokines and reduces HBsAg level in transgenic mice

Ist Teil von

• Chinese medical journal, 2012-09, Vol.125 (18), p.3266-3272

Ort / Verlag

China: Shanghai Public Health Clinical Center, Key Lab of Medical Molecular Virology, Shanghai Medical College, Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, China%International Joint Cancer Institute & Chinese People's Liberation Army General Hospital Cancer Center, Second Military Medical University, Shanghai 200433, China

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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. 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.