FimH as a mucosal adjuvant enhances persistent antibody response and protective efficacy of the anti-caries vaccine
FimH as a mucosal adjuvant enhances persistent antibody response and protective efficacy of the anti-caries vaccine
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FimH 作为粘膜佐剂可增强抗龋齿疫苗的持续抗体反应和保护功效
DOI：
10.1016/j.archoralbio.2019.02.009
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发表时间：
2019-05-01
影响因子：
3
通讯作者：
Li, Yu-Hong
中科院分区：
文献类型：
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作者：
Liu, Zhong-Fang;Chen, Jun-Lan;Li, Yu-Hong
目标：目的：研究重组沙门氏菌FimH S.T蛋白在体内外是否具有调节抗龋疫苗免疫应答的作用。流式细胞术、Real-time PCR和ELISA检测树突状细胞成熟标志物的表达和细胞因子的释放。另外，用抗龋PAc疫苗和FimH-S.T免疫BALB/c小鼠，ELISA法检测抗体应答。流式细胞仪检测免疫小鼠脾细胞对PAc抗原体外再处理的增殖反应。结果：纯化的FimH-S.T通过上调共刺激分子和MHC II的表达诱导DC 2. 4表型成熟，并通过TLR 4依赖的信号通路刺激细胞因子的产生和分泌。FimH-S.T与PAc的混合物免疫小鼠，可显著提高血清沿着唾液中PAc特异性抗体水平，促进脾细胞增殖。结论：重组FimH-S. T通过TLR 4信号通路激活DC 2. 4，具有黏膜佐剂作用，可增强抗龋疫苗的免疫保护作用。
Objective: To investigate whether the recombinant FimH-S.T protein could modulate immune response to anti-caries vaccine in vitro and in vivo.Design: Recombinant FimH protein derived from Salmonella was constructed and purified. The expression of dendritic cell maturation markers and cytokines release were performed by flow cytometry, Real-time PCR and ELISA. In addition, BALB/c mice were administered with anti-caries PAc vaccine plus FimH-S.T, antibody responses were evaluated by ELISA. Splenocytes of immunized mice were detected for their proliferative ability in response to in vitro retreatment with PAc antigen by flow cytometry. Caries protection against dental caries formation was also investigated.Results: The purified FimH-S.T induced phenotypic maturation of DC2.4 by up-regulating the expression of costimulatory molecules and MHC II, provoked the production and secretion of cytokines via TLR4-dependent signaling pathway in vitro. Furthermore, the mice immunized with the mixture of FimH-S.T and PAc significantly enhanced the PAc-specific antibodies in the serum along with saliva and promoted splenocyte proliferation. Our results also confirmed that PAc + FimH-S.T decreased the caries lesions formation which provided high protective efficacy against dental caries.Conclusion: Our study demonstrates that recombinant FimH-S.T could enhance specific IgA responses and protection of anti-caries vaccine, possessing mucosal adjuvant ability by activating DC2.4 via TLR4 signaling pathway.