PMID- 22964321
OWN - NLM
STAT- MEDLINE
DCOM- 20130213
LR  - 20120911
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Linking)
VI  - 125
IP  - 18
DP  - 2012 Sep
TI  - Immunization with HBsAg-Fc fusion protein induces a predominant production of Th1 
      cytokines and reduces HBsAg level in transgenic mice.
PG  - 3266-72
AB  - 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 alpha (TNF-alpha) 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.
FAU - Meng, Zhe-feng
AU  - Meng ZF
AD  - Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
FAU - Wang, Hua-jing
AU  - Wang HJ
FAU - Yao, Xin
AU  - Yao X
FAU - Wang, Xuan-yi
AU  - Wang XY
FAU - Wen, Yu-mei
AU  - Wen YM
FAU - Dai, Jian-xin
AU  - Dai JX
FAU - Xie, You-hua
AU  - Xie YH
FAU - Xu, Jian-qing
AU  - Xu JQ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Hepatitis B Surface Antigens)
RN  - 0 (Receptors, Fc)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/metabolism
MH  - Cytokines/*metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Hepatitis B Surface Antigens/genetics/*immunology/*metabolism
MH  - Immunity, Cellular/immunology
MH  - Immunity, Humoral/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Receptors, Fc/genetics/*immunology/*metabolism
MH  - Recombinant Fusion Proteins/genetics/*immunology/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2012/09/12 06:00
MHDA- 2013/02/14 06:00
CRDT- 2012/09/12 06:00
PHST- 2012/09/12 06:00 [entrez]
PHST- 2012/09/12 06:00 [pubmed]
PHST- 2013/02/14 06:00 [medline]
PST - ppublish
SO  - Chin Med J (Engl). 2012 Sep;125(18):3266-72.