Open AccessEnhanced efficacy of CTLA‐4 fusion anti‐caries DNA vaccines in gnotobiotic hamsters 1
Author(s) -
ZHANG Feng,
LI Yuhong,
FAN Mingwen,
JIA Rong,
XU Qingan,
GUO Jihua,
YU Fei,
TIAN Qiwei
Publication year - 2007
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2007.00600.x
Subject(s) - immunogenicity , dna vaccination , streptococcus mutans , antigen , antibody , immune system , biology , fusion protein , immunology , recombinant dna , t cell , cytotoxic t cell , microbiology and biotechnology , virology , in vitro , immunization , gene , bacteria , biochemistry , genetics
Aim: To evaluate the comparative immunogenicity and protective efficacy of the cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA‐4) fusion anti‐caries DNA vaccines pGJA‐P/VAX1, pGJA‐P, and non‐fusion anti‐caries DNA construct pGLUA‐P in hamsters. In addition, the ability of CTLA‐4 to target pGJA‐P/VAX1‐encoding antigen to dendritic cells was tested in vitro. Methods: All DNA constructs contain genes encoding the A‐P regions of a cell surface protein (PAc) and the glucan binding (GLU) domain of glucosyltransferases (GTFs) of cariogenic organism Streptococcus mutans. Human dendritic cells were mixed with the CTLA‐4‐Ig‐GLU‐A‐P 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 demonstrated that CTLA‐4‐Ig‐GLU‐A‐P protein was capable of binding to human dendritic cells. pGJA‐P/VAX1 and pGJA‐P induced significantly higher specific salivary and serum anti‐PAc antibody responses than pGLUA‐P. Significantly fewer caries lesions were also observed in hamsters immunized with pGJA‐P/VAX1 and pGJA‐P. There was no significant difference in the anti‐PAc antibody level or caries scores between pGJA‐P/VAX1 and pGJA‐P‐immunized groups. Conclusion: Antigen encoded by CTLA‐4 fusion anti‐caries DNA vaccine 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.