Tetraspanin 2-A (SjTsp2-A) gene was amplified by PCR. pcDNA3.1(+)/SjTsp2-A recombinant plasmids were constructed and transformed into E. coli DH5alpha. Twenty four BALB/c mice were randomly divided into pcDNA3.1(+)/ -SjTsp2-A group (A), pcDNA3.1(+)/SjGST group (B) and pcDNA3.1(+) group (C). Each mouse was injected through musculus quadriceps femoris by three times (two weeks interval) respectively with 100 microg pcDNA3.1(+)/SjTsp2-A, pcDNA3.1 (+)/SjGST, or pcDNA3.1(+). At two weeks after the final inoculation, mice were each challenged by 40 +/- 2 cercariae of S. japonicum. Forty-five days after infection, all mice were sacrificed, the number of worms collected and eggs in liver tissue was counted. Anti-pcDNA3.1(+)/SjTsp2-A antibody was detected by ELISA and protein expression in quadriceps muscle by immunohistochemical staining. The worm reduction rate (44.4%) and egg reduction rate (28.4%) of group A was higher than those of group B and C (P < 0.05), but no significant difference between groups B (3.9%, 19.3%) and C. Higher antibody titer (1:25 600) was detected in sera of group A. Immunohistochemistry analysis showed an expression of specific antigens in quadriceps muscles of groups A and B. The DNA candidate vaccine induces partial protective immunity against S japonicum in BALB/c mice.