Abstract: Objective To develop an anti-caries DNA vaccine-loaded Salmonella typhimurium(St) ghost and enhance the efficacy of immune responses induced by anti-caries DNA vaccine via mucosal route.Methods Both pREP4 and PhiX gene E expression plasmids were transformed into StJ357 and then induced with isopropyl β-D-1-thiogalactopyranoside (IPTG).The bacterial ghosts (BG) were collected after wash and loaded with anti-caries DNA vaccine pGJGLU/VAX.Mice were divided into four groups and immunized through the nasal route with pGJGLU/VAX-loaded BG(Group Ghost + pGJGLU/VAX),pVAX1-loaded BG (Group Ghost + pVAX1),pGJGLU/VAX-Bupivacaine complex (Group pGJGLU/VAX) and pVAX1-Bupivacaine complex (Group pVAX1),respectively.Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the immune responses.Results ELISA results showed that group Ghost + pGJGLU/ VAX had significantly higher level of specific anti-GLU SIgA antibody [(0.367 ± 0.086) A/μg] compared with group Ghost + pVAX1 [(0.122 ± 0.077) A/μg],Group pGJGLU/VAX [(0.068 ± 0.068) A/μg] or Group pVAX1 [(0.089 ±0.089) A/μg] (P =0.028,0.012 or 0.030,respectively).Conclusions St ghost was developed successfully,which enhanced the efficacy of immune responses induced by anti-caries DNA vaccine pGJGLU/VAX via the nasal route.