中科院武汉病毒研究所粘膜免疫学科组在防龋疫苗研究中又取得新进展。该学科组继（Journal of Dental Research）2012年91卷第3期正式发表龋齿疫苗粘膜佐剂研究进展后，又一防龋疫苗研究结果即将在最新一期（JDR，2012年91卷第10期）正式发表。
龋齿是人类最常见的细菌性慢性感染疾病之一，主要由变形链球菌附着和定植于牙齿表面，从而导致牙齿局部脱矿和钙化组织的破坏而形成。龋齿的发病率很高，可以发生在人的任何年龄段，给患者带来难以忍受的疼痛并严重影响身体健康。武汉病毒所鄢慧民研究员带领的研究团队致力于细菌鞭毛素蛋白（flagellin）相关的粘膜佐剂研究和应用，通过该蛋白与防龋DNA疫苗联合鼻腔免疫，成功诱导了较高水平的特异性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和龋齿的形成，证明了重组鞭毛素蛋白是一种有效的防龋粘膜免疫佐剂（JDR March 2012,vol. 91 no. 3,pp.249-254）。
在此基础上，该学科组采用了融合蛋白表达技术，将鞭毛素蛋白佐剂和龋齿疫苗抗原PAc融合表达为一个既包含粘膜佐剂又包含疫苗目标抗原的单个重组蛋白，并通过鼻腔粘膜免疫诱导产生了高效的特异抗体应答，尤其是口腔特异IgA抗体应答。实验证明，8.5微克剂量的重组蛋白疫苗滴鼻免疫即可让大鼠患龋程度降低64.2%，免疫保护效应比以往各种防龋疫苗大大提高，成为一个具有应用价值的新型防龋粘膜疫苗。
该研究得到了国家科技支撑计划（No. 2007BAI28B04）的支持。
Flagellin-PAc Fusion Protein is a High-efficacy Anti-caries Mucosal Vaccine
Y. Sun1,W. Shi1,J.Y. Yang1,D.H. Zhou1,Y.Q. Chen1,Y. Zhang1,Y. Yang1,B.X. He1,M.H. Zhong1,Y.M. Li1,Y. Cao1,Y. Xiao1,W. Li1,J. Yu1,Y.H. Li2,M.W. Fan2,H.M. Yan1,*
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.
