Self-assembling anticaries mucosal vaccine containing ferritin cage nanostructure and glucan-binding region of S. mutans glucosyltransferase effectively prevents caries formation in rodents
Self-assembling anticaries mucosal vaccine containing ferritin cage nanostructure and glucan-binding region of S. mutans glucosyltransferase effectively prevents caries formation in rodents
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含有铁蛋白笼纳米结构和变形链球菌葡萄糖基转移酶葡聚糖结合区的自组装防龋粘膜疫苗可有效预防啮齿动物龋齿形成
DOI：
10.1080/21645515.2017.1349046
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发表时间：
2017
影响因子：
4.8
通讯作者：
Ming-Wen Fan
中科院分区：
文献类型：
--
作者：
Xixi Cao;Yuhong Li;Qianlin Ye;Xuan Hu;Tianfeng Wang;Ming-Wen Fan
诱导粘膜免疫反应的抗肿瘤蛋白疫苗是无效的。因此，开发有效和方便的抗流感疫苗是牙科研究的重点。本研究通过将变形链球菌葡萄糖基转移酶（GLU）的葡聚糖结合区连接到铁蛋白的n端结构域，生成了自组装纳米颗粒，以确定这些新型纳米颗粒是否增强了啮齿动物抗GLU蛋白疫苗的免疫原性。我们构建了表达质粒pET28a-GLU-FTH，并采用大小排斥层析法从细菌中纯化蛋白。BALB/c小鼠被用来评估glu -铁蛋白（GLU-FTH）纳米颗粒诱导glu特异性粘膜和全身反应的能力。将glfth纳米颗粒与GLU单独或GLU与poly（I:C）的混合物在Wistar大鼠鼻内滴注后的保护效果进行比较。利用流式细胞术评估体外暴露于纳米颗粒的树突状细胞（DCs）的吞噬和成熟。与GLU或GLU与poly（I:C）的混合物相比，GLU- fth纳米颗粒疫苗诱导的GLU特异性抗体水平明显更高。与其他疫苗相比，接种GLU-FTH疫苗的龋齿评分较低。注射GLU-FTH纳米颗粒可增强树突状细胞的吞噬作用及其成熟。因此，自组装GLU-FTH是一种高效的抗粘膜疫苗，可增强抗体产生并抑制变形链球菌感染。
Anticaries protein vaccines that induce a mucosal immune response are not effective. Therefore, development of effective and convenient anticaries vaccines is a priority of dental research. Here we generated self-assembling nanoparticles by linking the glucan-binding region of Streptococcus mutans glucosyltransferase (GLU) to the N-terminal domain of ferritin to determine whether these novel nanoparticles enhanced the immunogenicity of an anticaries protein vaccine against GLU in rodents. We constructed the expression plasmid pET28a-GLU-FTH and purified the proteins from bacteria using sizeexclusion chromatography. BALB/c mice were used to evaluate the ability of GLU-ferritin (GLU-FTH) nanoparticles to induce GLU-specific mucosal and systemic responses. The protective efficiency of GLUFTH nanoparticles was compared with that of GLU alone or a mixture of GLU and poly(I:C) after administering an intranasal infusion to Wistar rats. The phagocytosis and maturation of dendritic cells (DCs) exposed in vitro to the nanoparticles were assessed using flow cytometry. The GLU-FTH nanoparticle vaccine elicited significantly higher levels of GLU-specific antibodies compared with GLU or a mixture of GLU and poly(I:C). Immunization with GLU-FTH achieved lower caries scores compared with those of the other vaccines. Administration of GLU-FTH nanoparticles enhanced phagocytosis by DCs and their maturation. Thus, self-assembling GLU-FTH is a highly effective anticaries mucosal vaccine that enhanced antibody production and inhibited S. mutans infection in rodents.