Suppression of immune response and protective immunity to a Japanese encephalitis virus DNA vaccine by coadministration of an IL-12-expressing plasmid

IL-12 plays a central role in both innate and acquired immunity and has bee n demonstrated to potentiate the protective immunity in several experimenta l vaccines. However, in this study, we show that IL-12 can be detrimental t o the immune responses elicited by a plasmid DNA vaccine. Coadministration of the IL-12-expressing plasmid (pIL-12) significantly suppressed the prote ctive immunity elicited by a plasmid DNA vaccine (pE) encoding the envelope protein of Japanese encephalitis virus. This suppressive effect was associ ated with marked reduction of specific T cell proliferation and Ab response s. A single dose of pIL-12 treatment with plasmid pE in initial priming res ulted in significant immune suppression to subsequent pE booster immunizati on. The pIL-12-mediated immune suppression was dose dependent and evident o nly when the IL-12 gene was injected either before or coincident with the p E DNA vaccine. Finally, using IFN-gamma gene-disrupted mice, we showed that the suppressive activity of the IL-12 plasmid was dependent upon endogenou s production of IFN-gamma. These results demonstrate that coexpression of t he IL-12 gene can sometimes produce untoward effects to immune responses, a nd thus its application as a vaccine adjuvant should be carefully evaluated .