title: In vivo engineering of a cellular immune response by coadministration of IL-12 expression vector with a DNA immunogen.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Kim
authors.forename: V
authors.initials: V
authors.lastname: Ayyavoo
authors.forename: M L
authors.initials: ML
authors.lastname: Bagarazzi
authors.forename: M A
authors.initials: MA
authors.lastname: Chattergoon
authors.forename: K
authors.initials: K
authors.lastname: Dang
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.forename: J D
authors.initials: JD
authors.lastname: Boyer
authors.forename: D B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D000818:Animals; D004279:DNA, Viral / Q000008:administration & dosage* / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000276:immunology; D015483:HIV Antibodies / Q000096:biosynthesis; D015497:HIV-1 / Q000276:immunology; D007111:Immunity, Cellular; D018664:Interleukin-12 / Q000008:administration & dosage / Q000096:biosynthesis* / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D004279:DNA, Viral; D015483:HIV Antibodies; D019444:Vaccines, DNA; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor