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In vivo engineering of a cellular immune response by coadministration of IL-12 expression vector with a DNA immunogen.

J J Kim, V Ayyavoo, M L Bagarazzi, M A Chattergoon, K Dang, B Wang, J D Boyer and D B Weiner
J Immunol January 15, 1997, 158 (2) 816-826;
J J Kim
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V Ayyavoo
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M L Bagarazzi
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M A Chattergoon
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K Dang
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B Wang
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J D Boyer
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D B Weiner
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Abstract

Recent studies support the importance of investigating a DNA vaccination approach for the immunologic control of HIV-1. In this regard, it may be important to specifically engineer immune responses in order to improve on first generation vaccine attempts. Especially for HIV, induction of cell-mediated immunity may be an important feature for any candidate vaccine. In an attempt to engineer in vivo the enhancement of cellular immune response and to direct Ag-dependent immune response from Th2 to Th1 type, we investigated the role of codelivery of genes for IL-12 and granulocyte-macrophage-CSF along with DNA vaccine formulations for HIV-1 Ag. We found that codelivery of IL-12 expression cassettes with DNA vaccines for HIV-1 in mice resulted in splenomegaly as well as a shift in the specific immune responses induced. The codelivery of IL-12 genes resulted in the reduction of specific Ab response, while the coinjection of granulocyte-macrophage-CSF genes resulted in the enhancement of specific Ab response. In addition, we observed a significant Ag-specific stimulation of T cells with codelivery of both cytokines. Most importantly, we observed a dramatic increase in specific CTL response from the group coimmunized with the HIV-1 DNA vaccine and IL-12 genes. This work demonstrates the power of DNA delivery in vivo for both the production of a new generation of more effective and targeted vaccines or immunotherapies as well as an analytic tool for the molecular dissection of the mechanisms of immune function.

  • Copyright © 1997 by American Association of Immunologists

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The Journal of Immunology
Vol. 158, Issue 2
15 Jan 1997
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In vivo engineering of a cellular immune response by coadministration of IL-12 expression vector with a DNA immunogen.
J J Kim, V Ayyavoo, M L Bagarazzi, M A Chattergoon, K Dang, B Wang, J D Boyer, D B Weiner
The Journal of Immunology January 15, 1997, 158 (2) 816-826;

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In vivo engineering of a cellular immune response by coadministration of IL-12 expression vector with a DNA immunogen.
J J Kim, V Ayyavoo, M L Bagarazzi, M A Chattergoon, K Dang, B Wang, J D Boyer, D B Weiner
The Journal of Immunology January 15, 1997, 158 (2) 816-826;
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Print ISSN 0022-1767        Online ISSN 1550-6606