Modulation of antigen-specific cellular immune responses to DNA vaccination in rhesus macaques through the use of IL-2, IFN-γ, or IL-4 gene adjuvants

Abstract

Extensive experiments have shown DNA vaccines' ability to elicit immune responses in vivo in a safe and well-tolerated manner in several model systems, including rodents and non-human primates. As the DNA-based vaccine and immunotherapy approaches are being explored in humans, significant efforts have also been focused on further improving the immune potency of this technology. One strategy to enhance immune responses for DNA vaccines is the use of molecular or genetic adjuvants. These molecular adjuvant constructs (which encodes for immunologically important molecules such as cytokines) can be co-administered along with DNA vaccine constructs. Once delivered, these adjuvants have shown to modulate the magnitude and direction (humoral or cellular) of the vaccine-induced immune responses in rodent models. To date, however, there has been very little data reported from studies in primates. In this study, we examined the effects of cytokine gene adjuvants to enhance the level of cell-mediated immune responses in rhesus macaques. We co-immunized rhesus macaques with expression plasmids encoding for IL-2, IFN-γ or IL-4 cytokines along with the DNA vaccine constructs encoding for HIV env/rev (pCEnv) and SIV gag/pol (pCSGag/pol) proteins. We observed that coadministration of IL-2 and IFN-γ cDNA resulted in enhancement of antigen-specific T cell-mediated immune responses.