Objective To evaluate the immunogenicity of hepatitis B core antigen(HBcAg)as well as its immunopotentiation to hepatitis B surface antigen(HBsAg).Methods The morphologies of HBcAg,HBsAg and virus-like particles(VLPs)of HBcAg+HBsAg were observed by electron microscopy.Mice were randomly divided into negative control(normal saline,NS),HBcAg(C),HBsAg(S),HBsAg+aluminum adjuvant(S+A)l,HBsAg+HBcAg(S+C)and HBsAg+HBcAg+aluminum adjuvant(S+C+A)l groups,and immunized i.m.with the corresponding antigens on days 0 and 14 respectively,of which the sera were collected and determined for anit-HBs,anti-HBc and antibody subclass against HBsAg.Meanwhile,the splenocytes of mice were collected and determined for IFNγ levels against HBsAg and HBcAg as well as IL-4 level against HBsAg.Results Elec-tron microscopy showed that both HBsAg and HBcAg formed VLPs with uniform structures,while the VLPs of mixed antigen were aggregated.The anti-HBs levels after the first immunization showed no significant difference in S+C and S groups(P = 0.074),while those after the second immunization were significantly higher in S+C group than in S group(P = 0.002).High anti-HBc levels were induced in both C and S+C groups.The antibody subclasses against HBsAg in S group were mainly IgG1,while those in S+C group were mainly IgG2a.The number of spots formed by IFNγ against HBsAg in S+C group was significantly larger than those in S,S+Al and S+C+Al groups(P 0.05).Both the numbers of spots formed by IFNγ against HBcAg were large in C and S+C groups.However,the numbers of spots formed by IL-4 against HBsAg were higher in S+C+Al group than in S+Al group(P = 0.026).Conclusion HBcAg showed good immunogenicity,which enhanced the immune response of HBsAg and promoted the Th1 polarization of the response.It laid a foundation of development of therapeutic HB vaccine.