Optimal vaccination against Schistosoma mansoni requires the induction of both B cell- and IFN-gamma-dependent effector mechanisms

Mice immunized with radiation-attenuated cercariae of Schistosoma mansoni d isplay resistance to challenge infection, which increases with multiple boo sting. Protection in animals receiving a single vaccination is thought to i nvolve a primarily cell-mediated, IFN-gamma-dependent mechanism, while humo ral immunity has been shown to contribute to challenge rejection in multipl y (three times) immunized mice. To better understand the respective contrib ution of the B lymphocyte and IFN-gamma-dependent effector arms in host res istance, we compared vaccine-induced immunity in B cell-deficient (mu MT) a nd IFN-gamma knockout (GKO) animals. Unexpectedly, after a single vaccinati on, B cell knockout (KO) mice displayed reduced protection against challeng e infection, although they developed a normal IFN-gamma-dominated cytokine response. This defect in resistance was equivalent to that displayed by GKO animals, Moreover, whereas two additional vaccinations significantly incre ased the level of immunity in wild-type mice, the protection in B cell KO a nimals remained unchanged. In contrast, multiple vaccination resulted in in creased but, nevertheless, defective resistance in GKO mice. Since FcR gamm a KO mice, which lack functional Fc gamma RI, Fc gamma RIII, and Fc epsilon RI, show no defects in vaccine-induced resistance after immunization eithe r one or three times, the B cell-dependent mechanism of protection involved does not appear to require FcR signaling, Together, these findings indicat e that effective vaccination against schistosomes depends on the simultaneo us induction of both humoral and cell-mediated immunity, a conclusion that may explain the limited success of most subunit vaccine protocols designed to preferentially induce either B cell- or IFN-gamma-dependent protective m echanisms.