DNA-mediated immunization in a transgenic mouse model of the hepatitis B surface antigen chronic carrier state.
Transgenic mice expressing the sequences coding for the envelope proteins of the hepatitis B virus (HBV) in the liver have been used as a model of the HBV chronic carrier state. We evaluated the possibility of inducing a specific immune response to the viral envelope antigens and thus potentially controlling chronic HBV infection. Using HBV-specific DNA-mediated immunization in this transgenic model, we show that the immune response induced after a single intramuscular injection of DNA resulted in the complete clearance of circulating hepatitis B surface antigen and in the long-term control of transgene expression in hepatocytes. This response does not involve a detectable cytopathic effect in the liver. Adoptive transfer of fractionated primed spleen cells from DNA-immunized mice shows that T cells are responsible for the down-regulation of HBV mRNA in the liver of transgenic mice. To our knowledge, this is the first demonstration of a potential immunotherapeutic application of DNA-mediated immunization against an infectious disease and raises the possibility of designing more effective ways of treating HBV chronic carriers.
Unité de Recombinaison et Expression Génétique, Institut National de la Santé et de la Recherche Médicale, U163, Institut Pasteur, Paris, France.
M
M
Mancini
M
M
Hadchouel
H L
HL
Davis
R G
RG
Whalen
P
P
Tiollais
M L
ML
Michel
D000818:Animals; D002353:Carrier State; D004279:DNA, Viral / Q000627:therapeutic use*; D005786:Gene Expression Regulation; D006509:Hepatitis B / Q000473:pathology / Q000628:therapy*; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics; D016233:Immunotherapy, Active / Q000379:methods*; D007700:Kinetics; D008099:Liver / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D010957:Plasmids / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D012333:RNA, Messenger; D012367:RNA, Viral; D014759:Viral Envelope Proteins