Cytokine molecular adjuvants modulate immune responses induced by DNA vaccine constructs for HIV-1 and SIV

DNA or nucleic acid immunization has been shown to induce both antigen-spec ific cellular and humoral immune responses in vivo. Moreover, immune respon ses induced by DNA immunization can be enhanced and modulated by the use of molecular adjuvants, To further engineer the immune response in vivo, we i nvestigated the induction and regulation of immune responses from the codel ivery of Th1 cytokines (interleukin-2 [IL-2] and IL-12), Th2 cytokines (IL- 4 and IL-10), and granulocyte-macrophage colony-stimulating factor (GM-CSF) genes along with a DNA vaccine construct encoding for simian immunodeficie ncy virus (SIV) gag/pol proteins. We observed that coinjection with IL-2, I L-4, IL-10, and GM-CSF resulted in increased levels of antigen-specific ant ibodies. In addition, we found that coinjection with cytokine genes drove t he immune responses toward a more Th1 or Th2 phenotype, We also observed th at coadministration of IL-2, IL-12, and GM-CSF genes resulted in a dramatic enhancement of Th proliferation responses. Moreover, coimmunization with I L-12 genes resulted in a dramatic enhancement of antigen-specific cytotoxic T lymphocyte (CTL) responses. These results support the potential utility of molecular adjuvants in DNA vaccine regimens.