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© Research
Publication : Hepatology (Baltimore, Md.)

Hepatitis B virus as a gene delivery vector activating foreign antigenic T cell response that abrogates viral expression in mouse models

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Hepatology (Baltimore, Md.) - 01 Nov 2009

Deng Q, Mancini-Bourgine M, Zhang X, Cumont MC, Zhu R, Lone YC, Michel ML

Link to Pubmed [PMID] – 19821533

Hepatology 2009 Nov;50(5):1380-91

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.

http://www.ncbi.nlm.nih.gov/pubmed/19821533