Specific IgG,IgG1,IgG2a,and sIgA,induced by the NMB0315 DNA vaccine(pNMB0315-CpG),protein NMB0315 vaccine(rNMB0315-FA),NMB0315 DNA vaccine prime-protein boost at week 8, were detected by indirect ELISA,the A450 values were up to(0. 505±0. 042,0. 513±0. 022,0. 342±0. 017,0. 250±0. 015),(0. 823± 0. 061,0. 807±0. 045,0. 596±0. 027,0. 450±0. 028)and(0. 694±0. 053,0. 711±0. 032,0. 455±0. 021,0. 386±0. 024)respectively, which was significantly higher than the PBS control(P<0. 05). The antibody level of proteinvaccine was significantly higher than the nucleic acid vaccine group and combined immunization group ( P<0. 05 ) . The stimulation index and IFN-γ level of combined immunization group were significantly higher than the proteinvaccine group and nucleic acid vaccine group(P<0. 05). The bactericidal titer of nucleic acid vaccine group, proteinvaccine group and combined immunization group reached 164, 1128 and 1128 respectively,and the protection rates were 70%,95% and 80% respectively. The IgG2a/IgG1 ratios of the nucleic acid vaccine group, the recombinant proteinvaccine group and the combined immunizationvaccine group were all less than 1 at week 2, 4, 6, 8.