The anti-miracidial potential of recombinant Schistosoma mansoni glutathione S-transferase 26 (rSmGST26) or native crude soluble egg antigens (SEA) was assessed. The associated dynamics of granuloma formation and immune responses were evaluated. Naive C57BL/6 mice were injected intravenously with multiple doses of either SEA (SEA-group) or rSmGST26 (GST-group) 7 days before cercarial infection. The immunized groups and the respective controls were sacrificed 6, 8 and 16 weeks postinfection (p.i.). Acceleration of ova destruction and reduction of granuloma diameter were greater in the GST-group than the SEA-group, mainly at 8 weeks p.i. However, the amelioration of hepatic pathology and function was more evident in the SEA-group. Concurrently, serum-specific IgG1 levels were elevated throughout the course of infection in the immunized groups compared to the infected controls. Initial rise of all splenic cytokines and serum anti-SEA IgE levels at 6 weeks p.i. was observed, followed by a dramatic drop in the levels of the proinflammatory cytokines IL-2, IFNgamma, IL-4 and TNF-alpha and IgE at 8 weeks of infection. IL-10 level was lower at 8 weeks p.i. than at 6 weeks, but was higher in immunized groups than in infected controls. Several responses may be implicated as an outcome of the present immunization protocol, such as increased levels of blocking antibody (IgG1) and IL-10 with decreased levels of proinflammatory cytokines and IgE.