Studies with double cytokine-deficient mice reveal that highly polarized Th1-and Th2-type cytokine and antibody responses contribute equally to vaccine-induced immunity to Schistosoma mansoni

A fundamental obstacle to vaccine development in schistosomiasis mansoni is a lack of understanding of what type of an immune response should be invok ed. We have addressed this central issue by using the radiation-attenuated cercariae vaccine in mice genetically engineered to exhibit highly polarize d type 1 (IL-10/IL-4-deficient) or type 2 (IL-10/IL-12-deficient) cytokine and Ab phenotypes, Our data show that while significant differences in immu nity exist after a single vaccination with irradiated cercariae in double c ytokine-deficient vs wild-type mice, these differences disappear after two vaccinations. The most important finding of these studies, however, was rev ealed in vaccinated IL-10-deficient mice. These mice developed a mixed and elevated type 1- and type 2-associated immune response and developed anti-s chistosome immunity at levels equal to or better than those in wild-type mi ce. This immunity in IL-10-deficient mice correlated with higher parasite-s pecific Ab titers, greater proliferative capacity of lymphocytes, increased frequency of IFN-gamma- and IL-4-secreting cells, elevated perivascular/pe ribronchial inflammatory responses in the lung, and greater in vitro schist osomulacidal capacity of parasite Ag-elicited cells. These results suggest that optimal vaccine-induced immunity against schistosomes is linked not to the development of a highly polarized response, but, rather, to the induct ion of both type 1- and type 2-associated immune responses.