The radiation-attenuated schistosome vaccine induces high levels of protective immunity in the absence of B cells.

Abstract

Radiation-attenuated cercariae of Schistosoma mansoni elicit consistently high levels of protective immunity in mice. The cell-mediated pulmonary effector mechanisms have been well characterized but the role of B cells and antibodies remains ill defined. We have compared the immune responses of B-cell-deficient (muMT) mice and their wild-type (WT) counterparts following exposure to the attenuated vaccine. Both groups mounted a T helper type 1 (Th1)-biased response in the skin-draining lymph nodes after vaccination. Interferon-gamma was the dominant cytokine secreted by airway leucocytes after challenge in both muMT and WT mice, but there was a somewhat greater Th2 component in the former animals. The cellular infiltrates observed in the airways, and the pulmonary effector foci, were of similar composition in the two groups although some large foci were present in the muMT mice. There was a marked dichotomy in the protection induced in muMT animals by a single vaccination, with two-thirds showing levels similar to their WT counterparts, demonstrating that cell-mediated mechanisms alone can provide adequate protection. The remaining muMT mice had a mean worm burden identical to that of their challenge controls. A possible explanation is that a proportion of the muMT animals have a genetic defect closely associated with the mu-heavy-chain locus on chromosome 12, which affects their ability to mount a protective cell-mediated response. Three vaccinations enhanced the immunity of WT animals, most likely by augmenting antibody-mediated mechanisms. In contrast, no enhancement was seen in muMT mice, suggesting that the cell-mediated response is not boosted by multiple exposures to attenuated larvae.