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The Journal of Immunology, Vol 158, Issue 2 816-826, Copyright © 1997 by American Association of Immunologists
ARTICLES |
JJ Kim, V Ayyavoo, ML Bagarazzi, MA Chattergoon, K Dang, B Wang, JD Boyer and DB Weiner
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA.
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.
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D. H. Barouch, S. Santra, T. D. Steenbeke, X. X. Zheng, H. C. Perry, M.-E. Davies, D. C. Freed, A. Craiu, T. B. Strom, J. W. Shiver, et al. Augmentation and Suppression of Immune Responses to an HIV-1 DNA Vaccine by Plasmid Cytokine/Ig Administration J. Immunol., August 15, 1998; 161(4): 1875 - 1882. [Abstract] [Full Text] [PDF]
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M. A. Chattergoon, T. M. Robinson, J. D. Boyer, and D. B. Weiner Specific Immune Induction Following DNA-Based Immunization Through In Vivo Transfection and Activation of Macrophages/Antigen-Presenting Cells J. Immunol., June 15, 1998; 160(12): 5707 - 5718. [Abstract] [Full Text] [PDF]
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W. M. Siders, P. W. Wright, J. A. Hixon, W. G. Alvord, T. C. Back, R. H. Wiltrout, and R. G. Fenton T Cell- and NK Cell-Independent Inhibition of Hepatic Metastases by Systemic Administration of an IL-12-Expressing Recombinant Adenovirus J. Immunol., June 1, 1998; 160(11): 5465 - 5474. [Abstract] [Full Text] [PDF]
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