Immunogenicity and protective efficacy of a targeted fusion DNA construct against dental caries.
Targeting antigens to antigen-presenting cells by fusion to cytotoxic T lymphocyte-associated antigen 4 (CTLA4) has been shown to be a highly efficient method to enhance the efficacy of DNA vaccines. The purpose of this study was to determine the immunogenicity and protective efficacy of the targeted fusion DNA construct pGJA-P, which contains the signal peptide and extracellular regions of human CTLA4 gene, the hinge and Fc regions of human Iggamma1 gene, the glucan-binding domain of the Streptococcus mutans gtfB gene and the A-P fragment of the S. mutans pac gene, compared with the fusion DNA construct pGLUA-P, which contains only the glucan-binding domain of the S. mutansgtfB gene and the A-P fragment of the S. mutans pac gene. BALB/c mice were immunized with pGJA-P, pGLUA-P, or pCI (vector) by the intramuscular or intranasal route. Specific anti-PAc and anti-GTF-I serum IgG and salivary IgA antibody responses were assessed by an enzyme-linked immunosorbent assay. Wistar rats were orally challenged with S. mutans and immunized with pGJA-P, pGLUA-P, or pCI intramuscularly or intranasally, and caries activity was evaluated by the Keyes method. pGJA-P induced accelerated and increased serum and salivary antibody responses in mice compared with pGLUA-P. Rats immunized with pGJA-P had significantly fewer caries lesions than rats immunized with pGLUA-P (p < 0.01). Thus, this study demonstrates that the targeted DNA construct pGJA-P can enhance both systemic and mucosal immunity and may be a useful strategy for improving the protective efficacy of anticaries DNA vaccines.
Xu
Qing-an
QA
Key Laboratory of Oral Biomedical Engineering, Stomatological College of Wuhan University, Wuhan, Hubei, China.
Yu
Fei
F
Fan
Mingwen
M
Bian
Zhuan
Z
Guo
Jihua
J
Jia
Rong
R
Chen
Zhi
Z
Peng
Bin
B
Fan
Bing
B
D000069594:Abatacept; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D003086:Bacteriocin Plasmids; D003731:Dental Caries / Q000517:prevention & control*; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017208:Rats, Wistar; D012463:Saliva / Q000276:immunology; D013290:Streptococcal Infections / Q000517:prevention & control*; D013295:Streptococcus mutans / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*
D018796:Immunoconjugates; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D000069594:Abatacept