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Division of Cancer Research and
Division of Clinical Research, Institute of Biomedical Sciences, Academia Sinica;
Graduate Institute of Life Sciences, National Defense Medical Center;
§
Graduate Institute of Clinical Medicine and
¶
Graduate Institute of Microbiology, National Taiwan University; and
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Development Center for Biotechnology, Taipei, Taiwan
In this study, we provide direct evidence that the magnitude and
nature of the immune response to a DNA vaccine can be differentially
regulated by codelivery of various mouse cytokine genes. Mice immunized
with a hepatitis B virus (HBV) DNA vaccine and the IL-12 or IFN-
gene exhibited a significant enhancement of Th1 cells and increased
production of anti-HBV surface IgG2a Ab, as well as a marked
inhibition of Th2 cells and decreased production of IgG1 Ab. In
contrast, coinjection of the IL-4 gene significantly enhanced the
development of specific Th2 cells and increased production of IgG1 Ab,
whereas Th1 differentiation and IgG2a production were suppressed.
Coinjection of the IL-2 or the granulocyte-macrophage-CSF gene enhanced
the development of Th1 cells, while the development of Th2 cells was
not affected, and the production of IgG1 and IgG2a Ab were both
increased. The CTL activity induced by HBV DNA vaccination was most
significantly enhanced by codelivery of the IL-12 or IFN- gene,
followed by the IL-2 or granulocyte-macrophage-CSF gene, whereas
codelivery of the IL-4 gene suppressed the activity. When challenged
with HBV surface Ag (HBsAg)-expressing syngeneic tumors, significant
reduction of tumor growth was observed in mice that were coadministered
the IL-12 gene but not the IL-4 gene. Taken together, these results
demonstrate that application of a cytokine gene in a DNA vaccine
formulation can influence the differentiation of Th cells as well as
the nature of an immune response and may thus provide a strategy to
improve its prophylactic and therapeutic efficacy.
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