Antigen-specific humoral and cellular immune responses can be modulated inrhesus macaques through the use of IFN-gamma, IL-12, or IL-18 gene adjuvants

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 engineer the immune response in vivo towards more T-helper (Th) 1-type cellular responses, we investigated the co-delivery of inteferon (IFN)-gamma, interleukin (IL)-12, and IL-18 genes along with DNA vaccine constructs. We observed that both antigen-specific humoral and cel lular immune responses call be modulated through the use of cytokine adjuva nts in mice. Most of this work has been performed in rodent models. There h as been little confirmation of this technology in primates. We also evaluat ed the immunomodulatory effects of this approach in rhesus macaques, since non-human primates represent the most relevant animal models for human immu nodeficiency virus (HIV) vaccine studies. As in the murine studies, we also observed that each Th1 cytokine adjuvant distinctively regulated the level of immune responses generated. Co-immunization of IFN-gamma and IL-18 in m acaques enhanced the level of antigen-specific antibody responses. Similarl y, co-delivery of IL-12 and IL-18 also enhanced the level of antigen-specif ic Th proliferative responses. These results extend this adjuvant strategy in a more relevant primate model and support the potential utility of these molecular adjuvants in DNA vaccine regimens.