Immunogenicity and protective efficacy of a targeted fusion DNA construct against 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 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.

• Authors: Qing-an Xu, Fei Yu, Mingwen Fan, Zhuan Bian, Jihua Guo, Rong Jia, Zhi Chen, Bin Peng, Bing Fan
• Journal: Caries research (Caries Res) 2005 Sep-Oct Vol. 39 Issue 5 Pg. 422-31 ISSN: 0008-6568 [Print] Switzerland
• PMID: 16110216 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2005 S. Karger AG, Basel.

Chemical References

• Immunoconjugates
• Immunoglobulin G
• Vaccines, DNA
• Abatacept

Topics

• Abatacept
• Animals
• Antigen-Presenting Cells (immunology)
• Bacteriocin Plasmids
• Dental Caries (prevention & control)
• Female
• Humans
• Immunoconjugates (genetics, immunology)
• Immunoglobulin G (blood)
• Mice
• Mice, Inbred BALB C
• Rats
• Rats, Wistar
• Saliva (immunology)
• Streptococcal Infections (prevention & control)
• Streptococcus mutans (immunology)
• Vaccines, DNA (immunology)