
Vol. 39, No. 5, 2005
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Original Paper
Immunogenicity and Protective Efficacy of a Targeted Fusion DNA Construct against Dental Caries
Qing-an Xu, Fei Yu, Mingwen Fan, Zhuan Bian, Jihua Guo, Rong Jia, Zhi Chen, Bin Peng, Bing Fan
Key Laboratory of Oral Biomedical Engineering, Stomatological College of Wuhan University, Wuhan, China
Address of Corresponding Author
Caries Res 2005;39:422-431 (DOI: 10.1159/000086851)
Key Words
- DNA Vaccines
- Antigen-presenting cells
- Streptococcus mutans
- Dental caries
Abstract
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 Ig 1 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. Copyright © 2005 S. Karger AG, Basel
Author Contacts
Prof. Mingwen Fan Stomatological College of Wuhan University Luoyu Road 237 430079 Wuhan, Hubei (China) Tel./Fax +86 27 87647443, E-Mail kqyywjtx@public.wh.hb.cn
Article Information
Q.-an Xu and F. Yu contributed equally to this work.
Received: May 25, 2004
Accepted after revision: February 4, 2005
Number of Print Pages : 10
Number of Figures : 5, Number of Tables : 0, Number of References : 35 |
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