DNA-Mediated Immunization in a Transgenic Mouse Model of the Hepatitis B Surface Antigen Chronic Carrier State
- Resource Type
- research-article
- Authors
- Mancini, Maryline; Hadchouel, Michelle; Davis, Heather L.; Whalen, Robert G.; Tiollais, Pierre; Michel, Marie-Louise
- Source
- Proceedings of the National Academy of Sciences of the United States of America, 1996 Oct . 93(22), 12496-12501.
- Subject
- Medical Sciences
Antigens
Mononuclear leukocytes
Liver
Spleen cells
Immunization
Antibodies
Hepatitis B virus
DNA
Messenger RNA
- Language
- English
- ISSN
- 00278424
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.