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Immunization with HBsAg-Fc fusion protein induces a predominant production of Th1 cytokines and reduces HBsAg level in transgenic mice.
MedLine Citation:
PMID:  22964321     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
Zhe-Feng Meng; Hua-Jing Wang; Xin Yao; Xuan-Yi Wang; Yu-Mei Wen; Jian-Xin Dai; You-Hua Xie; Jian-Qing Xu
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Chinese medical journal     Volume:  125     ISSN:  0366-6999     ISO Abbreviation:  Chin. Med. J.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7513795     Medline TA:  Chin Med J (Engl)     Country:  China    
Other Details:
Languages:  eng     Pagination:  3266-72     Citation Subset:  IM    
Affiliation:
Shanghai Public Health Clinical Center, Key Lab of Medical Molecular Virology, Shanghai Medical College, Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, China.
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