a The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine of Ministry of Education (KLOBM) , School & Hospital of Stomatology, Wuhan University , Wuhan , China.
b Department of Endodontics , School and Hospital of Stomatology, Wuhan University , Wuhan , China.
Hum Vaccin Immunother. 2017 Oct 3;13(10):2332-2340. doi: 10.1080/21645515.2017.1349046.
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 size-exclusion 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 GLU-FTH 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.
抗龋蛋白疫苗诱导黏膜免疫反应的效果并不理想。因此,开发有效且方便的抗龋疫苗是口腔医学研究的重点。在这里,我们通过将变异链球菌葡聚糖转移酶 (GLU) 的葡聚糖结合区与铁蛋白的 N 端结构域相连,生成了自组装纳米颗粒,以确定这些新型纳米颗粒是否能增强 GLU 抗龋蛋白疫苗在啮齿动物中的免疫原性。我们构建了表达质粒 pET28a-GLU-FTH,并使用排阻层析法从细菌中纯化了蛋白质。使用 BALB/c 小鼠评估 GLU-铁蛋白 (GLU-FTH) 纳米颗粒诱导 GLU 特异性黏膜和全身反应的能力。将 GLU-FTH 纳米颗粒的保护效率与 GLU 单独或 GLU 与聚肌苷酸 (poly(I:C)) 混合物经鼻内滴注给药后在 Wistar 大鼠中的效果进行了比较。使用流式细胞术评估了体外暴露于纳米颗粒的树突状细胞 (DC) 的吞噬作用和成熟情况。与 GLU 或 GLU 与 poly(I:C) 混合物相比,GLU-FTH 纳米疫苗诱导的 GLU 特异性抗体水平显著升高。与其他疫苗相比,GLU-FTH 免疫接种的龋齿评分较低。GLU-FTH 纳米颗粒的给药增强了 DC 的吞噬作用及其成熟。因此,自组装的 GLU-FTH 是一种高效的抗龋黏膜疫苗,可增强抗体产生并抑制变形链球菌在啮齿动物中的感染。