Aim:To evaluate the comparative immunogenicity and protective efficacy of thecytotoxic T-lymphocyte-associated antigen 4(CTLA-4)fusion anti-caries DNAvaccines pGJA-P/VAX1,pGJA-P,and non-fusion anti-caries DNA constructpGLUA-P in hamsters.In addition,the ability of CTLA-4 to target pGJA-P/VAX 1-encoding antigen to dendritic cells was tested in vitro.Methods:All DNAconstructs contain genes encoding the A-P regions of a cell surface protein(PAc)and the glucan binding(GLU)domain of glucosyltransferases(GTFs)of cari-ogenic organism Streptococcus mutans.Human dendritic cells were mixed withthe CTLA-4-Ig-GLU-A-P protein expressed by pGJA-P/VAX1-transfected cellsand analyzed by flow cytometry.Gnotobiotic hamsters were immunized with anti-caries DNA vaccines by intramuscular injection or intranasal administration.Antibody responses to a representative antigen PAc were assayed by ELISA,andcaries protection was evaluated by Keyes caries scores.Results:A flow cytometricanalysis demonstrated that CTLA-4-Ig-GLU-A-P protein was capable of bind-ing to human dendritic cells,pGJA-P/VAX1 and pGJA-P induced significantlyhigher specific salivary and serum anti-PAc antibody responses than pGLUA-ESignificantly fewer caries lesions were also observed in hamsters immunized withpGJA-P/VAX1 and pGJA-P.There was no significant difference in the anti-PAcantibody level or caries scores between pGJA-P/VAX1 and pGJA-P-immunizedgroups.Conclusion:Antigen encoded by CTLA-4 fusion anti-caries DNA vac-cine pGJA-P/VAX1 could specifically bind to human dendritic cells through theinteraction of CTLA-4 and B7 molecules.Fusing antigen to CTLA-4 has beenproven to greatly enhance the immunogenicity and protective efficacy of anti-caries DNA vaccines. Aim: To evaluate the comparative immunogenicity and protective efficacy of the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) fusion anti-caries DNAvaccines pGJA-P / VAX1, pGJA-P, and non-fusion anti-caries DNA constructpGLUA-P in hamsters. In addition, the ability of CTLA-4 to target pGJA-P / VAX 1-encoding antigen to dendritic cells was tested in vitro. Methods: All DNA constructs contain genes encoding the AP regions of a cell surface protein (PAc) and the glucan binding (GLU) domain of glucosyltransferases (GTFs) of cari-ogenic organism Streptococcus mutans. Human dendritic cells were mixed with the CTLA-4-Ig-GLU-AP protein expressed by pGJA-P / VAX1- transfected cells and analyzed by flow cytometry . Gnotobiotic hamsters were immunized with anti-caries DNA vaccines by intramuscular injection or intranasal administration. Antibody responses to a representative antigen PAc were assayed by ELISA, and caries protection was evaluated by Keyes caries scores. Results: A flow cytometric analysis of that C TLA-4-Ig-GLU-AP protein was capable of bind-ing to human dendritic cells, pGJA-P / VAX1 and pGJA-P induced significantlyhigher specific salivary and serum anti-PAc antibody responses than pGLUA-ESignificantly fewer caries lesions also also observed in hamsters immunized with pGJA-P / VAX1 and pGJA-P. There was no significant difference in the anti-PAcantibody level or caries scores between pGJA-P / VAX1 and pGJA-P-immunized groups. Conlusion: Antigen encoded by CTLA-4 fusion anti-caries DNA vac-cine pGJA-P / VAX1 could specifically bind to human dendritic cells through the interaction of CTLA-4 and B7 molecules. Fusing antigen to CTLA-4 has been proven to greatly enhance the immunogenicity and protective efficacy of anti-caries DNA vaccines.