Developing a vaccine against schistosomiasis would be an important advance on the control of this chronic and debilitating disease that afflicts millions of people worldwide. Herein we describe the use of the non-toxic B subunit of cholera toxin (CTB) genetically fused to Sm14 - a fatty-acid binding protein from Schistosoma mansoni - as an attempt to elicit a mucosal immune response against the lung stage of this parasite by intranasal immunization. Recombinant proteins were expressed on a prokaryotic system, purified by affinity chromatography and both immunochemically and spectroscopically characterized. Intranasal immunization experiments were performed on BALB/c mice and vaccine efficacy was assessed analyzing the worm-burden after challenge infection with S. mansoni cercariae. The results demonstrate that Sm14 itself was not able to reduce the worm burden on intranasally vaccinated animals. The presence of CTB - either in intranasal coadministration with or genetically fused to Sm14 - did not significantly improve the protective response of Sm14 as a worm burden reduction of only 20% could be observed. In addition to that, however, CTB demonstrated a clear anti inflammatory effect on the liver of immunized mice, which displayed hepatic granulomas around trapped eggs 15% smaller than control groups, indicating that CTB displays an immunomodulatory effect on the inflammatory responses induced by the parasite egg toxins. © 2010 Ramos HR, et al.