龋齿，俗称蛀牙，是人类最常见的细菌感染的慢性疾病之一，会导致牙齿局部脱矿和钙化组织的破坏。龋齿的发病率很高，可以在人一生的任何阶段发生，带来难以忍受的个人疼痛，已经造成了严重的社会负担。作为一种细菌性疾病，龋齿的病原体有多种，其中已经证明变形链球菌（Streptococcus mutans）是龋齿发生的主要病原体。变形链球菌的主要毒力因子是表面蛋白PAc和葡萄糖基转移酶GTF，研究人员已经针对毒力因子设计了防龋疫苗。作为一种预防手段，新型防龋DNA疫苗已在龋齿动物模型中证明有作用，但是由于其免疫原性比较弱，不能诱导充足的口腔分泌型免疫球蛋白A（S-IgA）抗体应答以有效抑制变形链球菌的定植来防止龋坏。
中科院武汉病毒研究所鄢慧民领导的研究团队针对上述主要问题，采用沙门氏菌来源的重组鞭毛素蛋白（Flagellin）作为粘膜佐剂，与防龋DNA疫苗联合鼻腔免疫，在大鼠龋齿模型中成功诱导较高特异性的血清抗体应答和唾液分泌型IgA应答，有效抑制了口腔变形链球菌的定植，显示出良好的龋齿保护效果。
该研究主要解决了有效诱导口腔特异IgA应答的关键问题，证明了重组鞭毛素蛋白是一种有效的防龋粘膜免疫佐剂，为防龋疫苗的应用奠定了一定基础。
该研究是与武汉大学口腔医学院合作，得到了国家科技支撑计划的支持，研究成果近期发表在牙医学研究的国际顶级期刊Journal of Dental Research 上,文章得到了JDR的主编William Giannobile的高度评价，同期配合发表了哈佛大学医学院福赛斯研究所的Daniel Smith教授专门撰写了评论文章。（生物谷Bioon.com）
doi:10.1177/0022034511424283
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Flagellin Enhances Saliva IgA Response and Protection of Anti-caries DNA Vaccine
W. Shi, Y. H. Li, F. Liu, J. Y. Yang, D. H. Zhou, Y. Q. Chen, Y. Zhang, Y. Yang, B. X. He, C. Han, M. W. Fan, H. M. Yan
We and others have shown that anti-caries DNA vaccines, including pGJA-P/VAX, are promising for preventing dental caries. However, challenges remain because of the low immunogenicity of DNA vaccines. In this study, we used recombinant flagellin protein derived from Salmonella (FliC) as a mucosal adjuvant for anti-caries DNA vaccine (pGJA-P/VAX) and analyzed the effects of FliC protein on the serum PAc-specific IgG and saliva PAc-specific IgA antibody responses, the colonization of Streptococcus mutans (S. mutans) on rat teeth, and the formation of caries lesions. Our results showed that FliC promoted the production of PAc-specific IgG in serum and secretory IgA (S-IgA) in saliva of rats by intranasal immunization with pGJA-P/VAX plus FliC. Furthermore, we found that enhanced PAc-specific IgA responses in saliva were associated with the inhibition of S. mutans colonization of tooth surfaces and endowed better protection with significant fewer caries lesions. In conclusion, our study demonstrates that recombinant FliC could enhance specific IgA responses in saliva and protective ability of pGJA-P/VAX, providing an effective mucosal adjuvant candidate for intranasal immunization of an anti-caries DNA vaccine.
