RT Journal Article
SR Electronic
T1 In vivo engineering of a cellular immune response by coadministration of IL-12 expression vector with a DNA immunogen.
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 816
OP 826
VO 158
IS 2
A1 Kim, J J
A1 Ayyavoo, V
A1 Bagarazzi, M L
A1 Chattergoon, M A
A1 Dang, K
A1 Wang, B
A1 Boyer, J D
A1 Weiner, D B
YR 1997
UL http://www.jimmunol.org/content/158/2/816.abstract
AB 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.