Immunogenicity and Protective Efficacy of a Targeted Fusion DNA Construct against Dental Caries
Immunogenicity and Protective Efficacy of a Targeted Fusion DNA Construct against Dental Caries
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DOI：
10.1159/000086851
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发表时间：
2005-08
期刊：
影响因子：
4.2
通讯作者：
Qing-an Xu;F. Yu;M. Fan;Z. Bian;Jihua Guo;R. Jia;Zhi Chen;B. Peng;B. Fan
中科院分区：
文献类型：
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作者：
Qing-an Xu;F. Yu;M. Fan;Z. Bian;Jihua Guo;R. Jia;Zhi Chen;B. Peng;B. Fan
通过与细胞毒性T淋巴细胞相关抗原4（CTLA 4）融合将抗原靶向抗原呈递细胞已被证明是增强DNA疫苗功效的高效方法。目的：研究含有人CTLA 4基因信号肽和胞外区、人IGγ1基因铰链区和Fc区、变形链球菌gtfB基因葡聚糖结合区和变形链球菌gtfB基因A-P片段的靶向融合DNA构建体pGJA-P的免疫原性和保护效果。pGLUA-P融合DNA构建体仅含有变形链球菌pac基因的葡聚糖结合结构域，而pGLUA-P融合DNA构建体仅含有变形链球菌pac基因的葡聚糖结合结构域。mutansgtfB基因和S.变形杆菌pac基因通过肌内或鼻内途径用pGJA-P、pGLUA-P或pCI（载体）免疫BALB/c小鼠。特异性抗-PAc和抗-GTF-I血清IgG和唾液伊加抗体应答通过酶联免疫吸附试验进行评估。Wistar大鼠经口感染S.用pGJA-P、pGLUA-P或pCI肌内或鼻内免疫变形链球菌，并通过Keyes方法评价龋齿活性。与pGLUA-P相比，pGJA-P可诱导小鼠血清和唾液中抗体应答的增加，且pGJA-P免疫的大鼠龋损明显少于pGLUA-P免疫的大鼠（p < 0.01）。因此，本研究表明，靶向DNA构建体pGJA-P可以增强全身和粘膜免疫，并可能是一个有用的策略，提高防龋DNA疫苗的保护效果。
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 Igγ1 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.