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DNA-mediated immunization in a transgenic mouse model of the hepatitis B surface antigen chronic carrier state.

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  • 1. Unité de Recombinaison et Expression Génétique, Institut National de la Santé et de la Recherche Médicale, U163, Institut Pasteur, Paris, France.
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    • Mancini M 1
    (1 author)

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Proceedings of the National Academy of Sciences of the United States of America, 01 Oct 1996, 93(22):12496-12501
https://doi.org/10.1073/pnas.93.22.12496 PMID: 8901610 PMCID: PMC38020

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Abstract 

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.

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Proc Natl Acad Sci U S A. 1996 Oct 29; 93(22): 12496–12501.
PMCID: PMC38020
PMID: 8901610

DNA-mediated immunization in a transgenic mouse model of the hepatitis B surface antigen chronic carrier state.

M Mancini, M Hadchouel, H L Davis, R G Whalen, P Tiollais, and M L Michel
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Abstract

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
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