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.
Mancini
M
M
Unité de Recombinaison et Expression Génétique, Institut National de la Santé et de la Recherche Médicale, U163, Institut Pasteur, Paris, France.
Hadchouel
M
M
Davis
H L
HL
Whalen
R G
RG
Tiollais
P
P
Michel
M L
ML
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