Activity and safety of DNA plasmids encoding IL-4 and IFN gamma

Cytokine-encoding DNA plasmids can act as 'genetic adjuvants: improving the immune response stimulated by co-administered DNA vaccines. We examined wh ether plasmids encoding the Th1 cytokine IFN gamma (pIFN gamma) or the Th2 cytokine IL-4 (pIL-4) have long-term effects on immune homeostasis when adm inistered to adult mice, or alter immune maturation in neonates. Both plasm ids boosted immunity against a co-administered vaccine, with pIFN gamma pro moting the development of a Th1 response (characterized by the production o f IgG2a antibodies), and pIL-4 preferentially stimulating a Th2 response (c haracterized by increased IgG1 antibody production). Both pIFN gamma and pI L-4 influenced the ratio of cells actively secreting Th1 versus Th2 cytokin es, consistent with an effect on Th cell maturation. Interestingly, this ef fect persisted for only a few weeks and was not magnified by repeated plasm id administration. Cytokine-encoding plasmids had no long-term effect on th e immune response of newborn or adult mice to subsequent antigenic stimulat ion, nor did they selectively induce the production of pathogenic anti-DNA autoantibodies. These results suggest cytokine-encoding plasmids may be saf e as immune adjuvants.