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鞭毛蛋白-PAc 融合蛋白是一种高效的抗龋黏膜疫苗。

Flagellin-PAc fusion protein is a high-efficacy anti-caries mucosal vaccine.

机构信息

Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China.

出版信息

J Dent Res. 2012 Oct;91(10):941-7. doi: 10.1177/0022034512457684. Epub 2012 Aug 14.

Abstract

We previously demonstrated that an anti-caries DNA vaccine intranasally administered with recombinant flagellin protein as a mucosal adjuvant enhanced salivary IgA response and conferred better protection against caries. However, the relatively weak immunogenicity of DNA vaccines and the necessity for a large quantity of antigens remain significant challenges. Here, we fused the flagellin derived from E. coli (KF) and target antigen PAc containing the A-P fragment of PAc from S. mutans (rPAc) to produce a single recombinant protein (KF-rPAc). The abilities of KF-rPAc to induce rPAc-specific mucosal and systemic responses and protective efficiency against caries following intranasal immunization were compared with those of rPAc alone or a mixture of rPAc and KF (KF + rPAc) in rats. Results showed that KF-rPAc promoted significantly higher rPAc-specific antibodies in serum as well as in saliva than did an equivalent dose of rPAc alone or a mixture of KF + rPAc. Intranasal immunization of 8.5 µg KF-rPAc could achieve 64.2% reduction of dental caries in rats. In conclusion, our study demonstrated that flagellin and PAc fusion strategy is promising for anti-caries vaccine development, and KF-rPAc could be used as an anti-caries mucosal vaccine.

摘要

我们之前证明,鼻内给予重组鞭毛蛋白作为黏膜佐剂的抗龋 DNA 疫苗可增强唾液 IgA 反应,并提供更好的防龋保护。然而,DNA 疫苗的相对较弱的免疫原性和大量抗原的需求仍然是重大挑战。在这里,我们将源自大肠杆菌的鞭毛蛋白(KF)和含有变形链球菌 PAc 的 A-P 片段的靶抗原 PAc(rPAc)融合,产生了一种单一的重组蛋白(KF-rPAc)。我们比较了 KF-rPAc 鼻内免疫后诱导 rPAc 特异性黏膜和系统反应以及抗龋保护效率的能力,与单独的 rPAc 或 rPAc 和 KF 的混合物(KF+rPAc)在大鼠中的能力。结果表明,与单独给予等量 rPAc 或 KF+rPAc 混合物相比,KF-rPAc 可显著促进血清和唾液中 rPAc 特异性抗体的产生。鼻内免疫 8.5 µg KF-rPAc 可使大鼠龋齿减少 64.2%。总之,我们的研究表明,鞭毛蛋白和 PAc 融合策略有望用于抗龋疫苗的开发,并且 KF-rPAc 可作为一种抗龋黏膜疫苗。

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