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Background: The host-interactive tegument of Schistosomes appears to be a successful strategy to survival in the blood stream involving in nutrition uptake and immune evasion.The outer-tegument membrane is dynamically replaced by a burst outward of membranous vacuoles that are synthesised in the cytons,and then pass to the tegument to fuse to the tegumental surface.Fusion of biological membranes is a fundamental process in all eukaryotic cells driven by formation of trans-SNARE complexes through pairing of vesicle associated v-SNAREs(VAMP)with complementary t-SNAREs on target membranes.The purpose of this study was to characterize Schistosomajaponicum vesicle-associated membrane protein 2(SjVAMP2)and to investigate its potential as a candidate vaccine against schistosomiasis.Methodology/Principal Findings: SjVAMP2 is member of the synaptobrevin superfamily.RT-PCR analysis revealed that significantly higher SjVAMP2 levels were observed in 28-and 42-day-old worms and SjVAMP2 expression was much higher in 42-day-old female worms than in those male worms.Furthermore,the expression levels in 28-and 42-day-old worms isolated from permissive host mice were significantly higher than in those isolated from less susceptible host rats.Additionally,the expression of SjVAMP2 was associated with membrane recovery in PZQ-treated worms.Immunofluorescence revealed that SjVAMP2 was mainly distributed in the tegument of the worms.Purified rSjVAMP2 emulsified with ISA206 adjuvant induced 34.7%and 16.4%reductions in worm burden,and 35.1%and 34.0%reductions in hepatic eggs in two independent trials.The IgG isotype and cytokine profile analysis demonstrated that rSjVAMP2 plus ISA206 immunization induced a mixed T helper(Th)1/Th2 response.Conclusion: Our study indicated that SjVAMP2 is a potential vaccine against S.japonicum and provides the basis for further investigations into the biological function of SjVAMP2.