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自转运蛋白 Ata 的一段短肽是一种有前途的保护性抗原,可用于预防 。

A Short Peptide of Autotransporter Ata Is a Promising Protective Antigen for Vaccination Against .

机构信息

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing, China.

School of Medicine, Tsinghua University, Beijing, China.

出版信息

Front Immunol. 2022 Apr 13;13:884555. doi: 10.3389/fimmu.2022.884555. eCollection 2022.

Abstract

With the emergence of multidrug-resistant strains, infection is becoming a thorny health problem in hospitals. However, there are no licensed vaccines against . trimeric autotransporter (Ata) is an important known virulence factor located on the outer membrane of bacteria. Herein, we carried out a series of experiments to test the immunogenicity of a short C-terminal extracellular region of Ata (Ata, only containing 39 amino acids) in a murine model. The short peptide Ata was fused with the cholera toxin B subunit (CTB), which has been reported to have immunoadjuvant activity. The fusion protein showed no inflammation and organ damages, and have the ability to elicit both Th1 and Th2 immune responses in mice. The bactericidal activities against and prophylactic effects of the fusion protein were further evidenced by a significant reduction in the bacterial load in the organs and blood. In addition, the candidate vaccine could provide broad protection against lethal challenges with a variety of strains. Moreover, when CpG was added on the basis of aluminum adjuvant, the immune response, especially cellular immunity, could be further strengthened. Overall, these results revealed that the Ata is a promising vaccine target against infection.

摘要

随着多药耐药菌株的出现,感染已成为医院的一个棘手的健康问题。然而,目前还没有针对的许可疫苗。三聚体自转运蛋白(Ata)是位于细菌外膜上的一个重要的已知毒力因子。在此,我们在小鼠模型中进行了一系列实验,以测试 Ata 的短胞外 C 端区域(Ata,仅含 39 个氨基酸)的免疫原性。短肽 Ata 与霍乱毒素 B 亚单位(CTB)融合,据报道 CTB 具有免疫佐剂活性。融合蛋白未引起炎症和器官损伤,并且能够在小鼠中引发 Th1 和 Th2 免疫反应。融合蛋白对和预防性作用的杀菌活性进一步通过器官和血液中细菌载量的显著减少得到证实。此外,该候选疫苗可以针对多种菌株的致死性挑战提供广泛的保护。此外,在铝佐剂的基础上添加 CpG 时,免疫反应,特别是细胞免疫,可以进一步增强。总的来说,这些结果表明 Ata 是针对感染的一种很有前途的疫苗靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5d0/9043751/217cef77001d/fimmu-13-884555-g001.jpg

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