武漢病毒研究所粘膜免疫學科組在防齲疫苗研究中又取得新進展,。最新防齲疫苗研究結果即將在最新一期（JDR,，2012年91卷第10期）正式發(fā)表,。
齲齒是人類最常見的細菌性慢性感染疾病之一,，主要由變形鏈球菌附著和定植于牙齒表面,，從而導致牙齒局部脫礦和鈣化組織的破壞而形成,。齲齒的發(fā)病率很高,，可以發(fā)生在人的任何年齡段,，給患者帶來難以忍受的疼痛并嚴重影響身體健康。武漢病毒研究所鄢慧民研究員帶領的研究團隊致力于細菌鞭毛素蛋白（flagellin）相關的粘膜佐劑研究和應用,，通過該蛋白與防齲DNA疫苗聯(lián)合鼻腔免疫,，成功誘導了較高水平的特異性血清抗體應答和唾液分泌型IgA應答，有效抑制了口腔變形鏈球菌的定植和齲齒的形成,，證明了重組鞭毛素蛋白是一種有效的防齲粘膜免疫佐劑（JDR March 2012,vol. 91 no. 3,pp.249-254）,。在此基礎上，該學科組采用了融合蛋白表達技術,，將鞭毛素蛋白佐劑和齲齒疫苗抗原PAc融合表達為一個既包含粘膜佐劑又包含疫苗目標抗原的單個重組蛋白,，并通過鼻腔粘膜免疫誘導產(chǎn)生了高效的特異抗體應答，尤其是口腔特異IgA抗體應答,。實驗證明8.5微克劑量的重組蛋白疫苗滴鼻免疫即可讓大鼠患齲程度降低64.2%,，免疫保護效應比以往各種防齲疫苗大大提高,，成為一個具有應用價值的新型防齲粘膜疫苗(JDR October 2012,vol.91 no.10 pp.941-947)。
該研究得到了國家科技支撐計劃（No. 2007BAI28B04）的支持,。（生物谷Bioon.com）
doi: 10.1177/0022034512457684
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Flagellin-PAc Fusion Protein is a High-efficacy Anti-caries Mucosal Vaccine
Sun Y, Shi W, Yang JY, Zhou DH, Chen Y, Zhang Y, Yang Y, He BX, Zhong MH, Li YM, Cao Y, Xiao Y, Li W, Yu J, Li YH, Fan MW, Yan H.
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.
