齲齒，俗稱蛀牙，是人類最常見的細(xì)菌感染的慢性疾病之一,，會導(dǎo)致牙齒局部脫礦和鈣化組織的破壞,。齲齒的發(fā)病率很高,，可以在人一生的任何階段發(fā)生，帶來難以忍受的個人疼痛,，已經(jīng)造成了嚴(yán)重的社會負(fù)擔(dān),。作為一種細(xì)菌性疾病，齲齒的病原體有多種,，其中已經(jīng)證明變形鏈球菌（Streptococcus mutans）是齲齒發(fā)生的主要病原體,。變形鏈球菌的主要毒力因子是表面蛋白PAc和葡萄糖基轉(zhuǎn)移酶GTF，研究人員已經(jīng)針對毒力因子設(shè)計了防齲疫苗,。作為一種預(yù)防手段,，新型防齲DNA疫苗已在齲齒動物模型中證明有作用，但是由于其免疫原性比較弱,，不能誘導(dǎo)充足的口腔分泌型免疫球蛋白A（S-IgA）抗體應(yīng)答以有效抑制變形鏈球菌的定植來防止齲壞,。
中科院武漢病毒研究所鄢慧民領(lǐng)導(dǎo)的研究團(tuán)隊針對上述主要問題，采用沙門氏菌來源的重組鞭毛素蛋白（Flagellin）作為粘膜佐劑,，與防齲DNA疫苗聯(lián)合鼻腔免疫,，在大鼠齲齒模型中成功誘導(dǎo)較高特異性的血清抗體應(yīng)答和唾液分泌型IgA應(yīng)答,，有效抑制了口腔變形鏈球菌的定植,，顯示出良好的齲齒保護(hù)效果。
該研究主要解決了有效誘導(dǎo)口腔特異IgA應(yīng)答的關(guān)鍵問題,，證明了重組鞭毛素蛋白是一種有效的防齲粘膜免疫佐劑,，為防齲疫苗的應(yīng)用奠定了一定基礎(chǔ)。
該研究是與武漢大學(xué)口腔醫(yī)學(xué)院合作,，得到了國家科技支撐計劃的支持,，研究成果近期發(fā)表在牙醫(yī)學(xué)研究的國際頂級期刊Journal of Dental Research 上,文章得到了JDR的主編William Giannobile的高度評價，同期配合發(fā)表了哈佛大學(xué)醫(yī)學(xué)院福賽斯研究所的Daniel Smith教授專門撰寫了評論文章,。（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.
