Muscle-specific expression of hepatitis B surface antigen: no effect on DNA-raised immune responses.
The injection of plasmid DNA encoding hepatitis B virus (HBV) envelope proteins in mouse muscle leads to the induction of specific humoral and cellular immune responses. Most studies on DNA-based immunization have used viral promoters to drive antigen expression. In this study, we compared the efficiency of a muscle-specific promoter, the human desmin gene promoter, with the commonly used cytomegalovirus (CMV) early gene promoter. We showed that increased in vitro expression of HBV envelope proteins from the human desmin gene promoter has no effect on the in vivo immune response even after the injection of as little as 10 micrograms of DNA. The injection of vectors encoding HBV envelope proteins under the control of either the human desmin gene promoter or the CMV promoter induced humoral and cytotoxic immune responses at comparable levels and of the same duration. The recruitment of antigen-presenting cells to the DNA injection site by pretreatment of muscle with a necrotizing agent increases the precocity and the intensity of the responses, particularly when the nonspecific CMV vector was used.
Unité de Recombinaison et Expression Génétique, INSERM U.163, Institut Pasteur, 28 rue du Docteur Roux, Paris Cédex 15, 75724, France.
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D
Loirat
Z
Z
Li
M
M
Mancini
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P
Tiollais
D
D
Paulin
M L
ML
Michel
D000818:Animals; D002460:Cell Line; D006510:Hepatitis B Antibodies / Q000096:biosynthesis; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007700:Kinetics; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D012038:Regeneration; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D019444:Vaccines, DNA / Q000276:immunology*
D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D019444:Vaccines, DNA