PMID- 19821533
OWN - NLM
STAT- MEDLINE
DCOM- 20091203
LR  - 20130520
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Linking)
VI  - 50
IP  - 5
DP  - 2009 Nov
TI  - Hepatitis B virus as a gene delivery vector activating foreign antigenic T cell 
      response that abrogates viral expression in mouse models.
PG  - 1380-91
LID - 10.1002/hep.23150 [doi]
AB  - Chronic hepatitis B virus (HBV) infection is characterized by functionally 
      impaired T cell responses. To ensure active immunotherapy, the immune response 
      must be switched from exhausted T cells to functional effectors that can attain 
      the liver and cure the viral infection. We thus designed a recombinant HBV (rHBV) 
      containing a modified viral core gene that specifically delivers a foreign 
      antigenic polyepitope to the liver. This recombinant virus could only be 
      self-maintained in hepatocytes already infected by HBV through capsid 
      complementation. A strong foreign epitope-specific T cell response was first 
      primed in the periphery by way of DNA immunization in human leukocyte antigen 
      (HLA)-A2/DR1 transgenic mice. After the hydrodynamic (hyd.) injection of rHBV, 
      expression of the foreign antigenic polyepitope in hepatocytes 
      attracted/reactivated a vigorous T cell response in situ. Most liver-infiltrating 
      CD8(+) T cells proved to be functional effectors. Following DNA priming and hyd. 
      injection, the rHBV-based expression of hepatitis B surface antigen (HBsAg) in 
      mouse liver was almost completely inhibited without causing major liver injury. 
      Studies in HBsAg/HLA-A2/DR1 transgenic mice further validated our approach. 
      CONCLUSION: For the first time, HBV was used as a gene delivery vector, which 
      strongly triggered functional T cell response and subsequently controlled the 
      viral expression in the liver of surrogate mouse models for HBV infection. It 
      might represent an innovative and promising strategy of active immunotherapy 
      during HBV persistent infection. This concept could even be more generally 
      extended to other chronic viral diseases.
FAU - Deng, Qiang
AU  - Deng Q
AD  - Laboratoire Pathogenese des Virus de l'Hepatite B, Institut Pasteur, Paris, 
      France.
FAU - Mancini-Bourgine, Maryline
AU  - Mancini-Bourgine M
FAU - Zhang, Xiaoming
AU  - Zhang X
FAU - Cumont, Marie-Christine
AU  - Cumont MC
FAU - Zhu, Ren
AU  - Zhu R
FAU - Lone, Yu-Chun
AU  - Lone YC
FAU - Michel, Marie-Louise
AU  - Michel ML
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Antigens)
RN  - 0 (Epitopes)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (HLA-DR1 Antigen)
RN  - 0 (Hepatitis B Surface Antigens)
SB  - IM
MH  - Animals
MH  - Antigens/*metabolism
MH  - Disease Models, Animal
MH  - Epitopes/genetics
MH  - Female
MH  - Gene Expression Regulation, Viral/*physiology
MH  - *Gene Transfer Techniques
MH  - Genetic Vectors/*genetics
MH  - HLA-A2 Antigen/genetics/metabolism
MH  - HLA-DR1 Antigen/genetics/metabolism
MH  - Hepatitis B Surface Antigens/genetics/metabolism
MH  - Hepatitis B virus/*genetics/physiology
MH  - Hepatitis C, Chronic/genetics/immunology/pathology
MH  - Immunotherapy, Active
MH  - Liver/immunology/pathology/virology
MH  - Mice
MH  - Mice, Transgenic
MH  - T-Lymphocytes/*immunology/pathology
MH  - Virus Replication/physiology
EDAT- 2009/10/13 06:00
MHDA- 2009/12/16 06:00
CRDT- 2009/10/13 06:00
PHST- 2009/10/13 06:00 [entrez]
PHST- 2009/10/13 06:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
AID - 10.1002/hep.23150 [doi]
PST - ppublish
SO  - Hepatology. 2009 Nov;50(5):1380-91. doi: 10.1002/hep.23150.