IL-12 ENHANCES VACCINE-INDUCED IMMUNITY TO SCHISTOSOMES BY AUGMENTINGBOTH HUMORAL AND CELL-MEDIATED IMMUNE-RESPONSES AGAINST THE PARASITE

The production of Th1-type cytokines is associated with:strong cell-me diated immunity, while Th2-type cytokines typically dominate humoral i mmune responses. In mice vaccinated a single time with attenuated cerc ariae of Schistosoma mansoni, the protection induced is associated wit h Th1 cytokine-dependent, cell-mediated immunity. In contrast, mice va ccinated multiple times display a more Th2-type dominant cytokine resp onse and develop Ab-dependent resistance. We have previously shown tha t IL-12 enhances cell-mediated immunity in singly vaccinated mice, In the present study, we asked what effects administering IL-12 as an adj uvant would have on the development of a protective humoral response i n multiply immunized animals. We found that multiply immunized/lL-12-t reated mice displayed a marked increase in resistance to challenge inf ection, with some animals demonstrating complete protection. The IL-12 -vaccinated mice developed strongly polarized Th1 responses but, impor tantly, also showed significant increases In parasite-specific Ab and, in particular, IgG2a, IgG26, and IgG1 isotypes. Passive transfer demo nstrated an enhanced ability of serum from these animals to protect na ive recipients. In addition, animals vaccinated in the presence of IL- 12 also developed macrophages with increased nitric oxide-dependent ki lling activity against the parasites. Together, these data demonstrate that IL-12, initially described as an adjuvant for cell-mediated immu nity, may be used to simultaneously to promote both humoral and cell-m ediated protective responses against infection.