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变形链球菌谷氨酸结合蛋白(GlnH)作为黏膜抗龋疫苗的抗原靶标。

Streptococcus mutans glutamate binding protein (GlnH) as antigen target for a mucosal anti-caries vaccine.

机构信息

Department of Microbiology, Biomedical Science Institute, University of São Paulo, São Paulo, SP, 137405508-900s, Brazil.

出版信息

Braz J Microbiol. 2022 Dec;53(4):1941-1949. doi: 10.1007/s42770-022-00823-0. Epub 2022 Sep 13.

Abstract

BACKGROUND

In recent years, several studies have demonstrated that bacterial ABC transporters present relevant antigen targets for the development of vaccines against bacteria such as Streptococcus pneumoniae and Enterococcus faecalis. In Streptococcus mutans, the glutamate transporter operon (glnH), encoding an ABC transporter, is associated with acid tolerance and represents an important virulence-associated factor for the development of dental caries.

RESULTS

In this study, we generated a recombinant form of the S. mutans GlnH protein (rGlnH) in Bacillus subtilis. Mice immunized with this protein antigen elicited strong antigen-specific antibody responses after sublingual administration of a vaccine formulation containing a mucosal adjuvant, a non-toxic derivative of the heat-labile toxin (LTK63) originally produced by enterotoxigenic Escherichia coli (ETEC) strains. Serum anti-rGlnH antibodies reduced adhesion of S. mutans to the oral cavity of naïve mice. Moreover, mice actively immunized with rGlnH were partially protected from oral colonization after exposure to the S. mutans NG8 strain.

CONCLUSIONS

Our results indicate that S. mutans rGlnH is a potential target antigen capable of inducing specific and protective antibody responses after immunization. Overall, these observations raise the prospect of the development of mucosal anti-caries vaccines.

摘要

背景

近年来,多项研究表明,细菌 ABC 转运蛋白是针对肺炎链球菌和粪肠球菌等细菌开发疫苗的重要抗原靶标。在变形链球菌中,谷氨酸转运子操纵子(glnH)编码一种 ABC 转运蛋白,与耐酸有关,是导致龋齿发生的重要毒力相关因素。

结果

本研究在枯草芽孢杆菌中生成了重组形式的变形链球菌 GlnH 蛋白(rGlnH)。用含有黏膜佐剂的疫苗制剂(一种最初由产肠毒素大肠杆菌(ETEC)菌株产生的不耐热毒素 LTK63 的无毒衍生物)经舌下途径给小鼠免疫后,该蛋白抗原能引发强烈的抗原特异性抗体应答。血清抗 rGlnH 抗体可减少变形链球菌对无菌小鼠口腔的黏附。此外,用 rGlnH 主动免疫的小鼠在接触变形链球菌 NG8 株后,口腔定植得到部分保护。

结论

我们的结果表明,变形链球菌 rGlnH 是一种潜在的靶抗原,免疫后能诱导特异性和保护性抗体应答。总的来说,这些观察结果提出了开发黏膜抗龋疫苗的前景。

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