An IL-12-based vaccine approach for preventing immunopathology in schistosomiasis.

Schistosomiasis is a major parasitic disease of developing countries. Pathology in schistosome infection is caused by the host granulomatous response to parasite eggs deposited in the tissues and the ensuing fibrosis. Previous work established that Th2 CD4+ cells play a major role in expanding granulomatous lesions and in fibrosis in murine models. We have used IL-12 both therapeutically to downmodulate this response and as an adjuvant with egg antigens to prevent pathology after subsequent parasite challenge. These effects appears to rely on the induction of IFN-gamma by the injected IL-12. Interestingly, while IL-12 treatment or vaccination downregulates most egg-specific Th2 cytokine responses, IL-10 production in vivo is enhanced. Because we have also shown that IL-12 can be used as an adjuvant to augment protective immunity against this helminth, it may be possible to design a combined parasite Ag/IL-12 vaccine which both limits infection and blocks the tissue pathology caused by eggs of worms escaping the resistance mechanisms evoked by immunization. At a more general level, our results demonstrate the potential of IL-12-based vaccine strategies to block Th2-dependent disease processes including allergy.