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Optimal Vaccination Against Schistosoma mansoni Requires the Induction of Both B Cell- and IFN--Dependent Effector Mechanisms

Dragana Jankovic^1,*, Thomas A. Wynn^*, Marika C. Kullberg^*, Sara Hieny^*, Patricia Caspar^*, Stephanie James^*, Allen W. Cheever^*, and Alan Sher^*

^* Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Biomedical Research Institute, Rockville, MD 20852

Mice immunized with radiation-attenuated cercariae of Schistosoma mansoni display resistance to challenge infection, which increases with multiple boosting. Protection in animals receiving a single vaccination is thought to involve a primarily cell-mediated, IFN--dependent mechanism, while humoral immunity has been shown to contribute to challenge rejection in multiply (three times) immunized mice. To better understand the respective contribution of the B lymphocyte- and IFN--dependent effector arms in host resistance, we compared vaccine-induced immunity in B cell-deficient (µMT) and IFN- knockout (GKO) animals. Unexpectedly, after a single vaccination, B cell knockout (KO) mice displayed reduced protection against challenge infection, although they developed a normal IFN--dominated cytokine response. This defect in resistance was equivalent to that displayed by GKO animals. Moreover, whereas two additional vaccinations significantly increased the level of immunity in wild-type mice, the protection in B cell KO animals remained unchanged. In contrast, multiple vaccination resulted in increased but, nevertheless, defective resistance in GKO mice. Since FcR KO mice, which lack functional FcRI, FcRIII, and FcRI, show no defects in vaccine-induced resistance after immunization either one or three times, the B cell-dependent mechanism of protection involved does not appear to require FcR signaling. Together, these findings indicate that effective vaccination against schistosomes depends on the simultaneous 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--dependent protective mechanisms.

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