Abstract Objective:To observe and confirm the specific humoral and cellurar immune responses induced by the nucleic acid vaccinesencoding HBV PreS2+S of subtypes adw and adr and encoding HBcAg in H-2b mice. Methods: Twenty-three C57BL/6 (H-2b) mice were ran-domly divided into four groups:group pJW4303(group P); group pJW4303/MHBs/adw(group W); group pJW4303/MHBs/adr(group R) andgroup pJW4303/MHBs/adr+pJW4303/HBc(group R+C) .The imunization method is that each mouse was injected(i.m) into the quadriceps femurs muscles with the corresponding 100?g(100?l) of plasmid DNA at 0,2,4 w.ELISA determined the level of anti-HBs and anti-HBc an-tibody in each mouse sera and the concentrations of IEN-? and IL-4 culture supernatant of spleen cells.Antigen specific proliferation of mousesplenocytes was measured by 3 H-TdR incorporating assay and the stimulation index(SI) was calculated.Results:After the last immunization,anti-HBs antibody had been detected in all mice of group W,group R and group R+C.The titers of anti-HBs were ranged from 22 329 to665.5 mU/ml.There are very significant differences between DNA vaccine groups (group W,group R,group R+C) and control group (groupP)(P0.05).Anti-HBs was first de-tected in group R+C.After the first immunization of nucleic acid vaccine of pJW4303/HBc,anti-HBc antibody appeared in all mice of groupR+C. Neither anti-HBs nor anti-HBc antibody appeared in all nice of group R+C.Neither anti-HBs nor anti-HBc was detected in group P.The stimulation index(SI) represent the capacity of antigen specific mouse proliferation of splenocytes. HBsAg-specific SIs of mouse splenocytesfrom group W,group R and group R+C is hipe than that in group P(P