In Vivo Engineering of a Cellular Immune Response by Coadministration of IL-12 Expression Vector with a DNA Immunogen

Jong J. Kim, Velpandi Ayyavoo, Mark L. Bagarazzi, Michael A. Chattergoon, Kesan Dang, Bin Wang, Jean D. Boyer, David B. Weiner

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)816-826
Number of pages11
JournalJournal of Immunology
Volume158
Issue number2
StatePublished - Jan 15 1997
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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