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鉴定土壤传播性蠕虫和曼氏血吸虫蛋白质组中的抗原线性肽。

Identification of antigenic linear peptides in the soil-transmitted helminth and Schistosoma mansoni proteome.

机构信息

Department of Virology, Parasitology, Immunology and Physiology, Ghent University, Merelbeke, Belgium.

Global Public Health R&D, Janssen Pharmaceutica NV, Beerse, Belgium.

出版信息

PLoS Negl Trop Dis. 2021 Apr 28;15(4):e0009369. doi: 10.1371/journal.pntd.0009369. eCollection 2021 Apr.

Abstract

The scientific community identified non stool-based biomarkers as the way forward to support soil-transmitted helminth (STH; Ascaris lumbricoides, Trichuris trichiura and the hookworms Ancylostoma duodenale and Necator americanus) and schistosome (S. mansoni and S. haematobium) deworming programs. This support is needed in making the decision of whether or not to stop preventive chemotherapy intervention efforts and to ultimately transition towards a post-intervention surveillance phase. We applied a two-step micro-array approach to identify antigenic linear epitopes in the STH and S. mansoni proteomes. In a first experiment, we identified antigenic peptides by applying sera from 24 STH and/or S. mansoni infected Ethiopian children on a high-density peptide microarray containing 3.3 million peptides derived from the complete STH and S. mansoni proteomes. A second array experiment with 170,185 peptides that were recognized in the first array was designed to identify non-specific antibody reactivity by applying sera from 24 healthy individuals from Belgium (a non-endemic country). From this array testing cascade, several peptides were identified for STH but none of them appeared to be unique for one species. We therefore concluded that for STH, none of the peptides revealed to be sufficiently sensitive or species specific. For S. mansoni, some promising peptides were identified prompting future investigation. Based on these results, it is unlikely that linear epitopes would be highly useful in detecting species-specific antibody responses to STH in endemic communities. For S. mansoni, one particular peptide of the micro-exon gene 12 (MEG-12) protein deserves further research. In addition, this study emphasizes the need of well-characterized biobanks for biomarker discovery, particularly when the integration of multiple disease programs is envisioned.

摘要

科学界已将非粪便生物标志物确认为支持土源性蠕虫(STH;蛔虫、鞭虫和十二指肠钩虫和美洲板口线虫)和血吸虫(曼氏血吸虫和埃及血吸虫)驱虫方案的未来方向。这是在决定是否停止预防性化疗干预措施以及最终过渡到干预后监测阶段时所必需的支持。我们应用两步微阵列方法来鉴定 STH 和 S. mansoni 蛋白质组中的抗原线性表位。在第一个实验中,我们通过应用来自 24 名 STH 和/或 S. mansoni 感染的埃塞俄比亚儿童的血清,在包含源自完整 STH 和 S. mansoni 蛋白质组的 330 万个肽的高密度肽微阵列上鉴定抗原肽。第二个阵列实验设计了 170,185 个肽,这些肽在第一个阵列中被识别出来,目的是通过应用来自比利时(非流行国家)的 24 名健康个体的血清来鉴定非特异性抗体反应。通过这个阵列测试级联,鉴定了一些用于 STH 的肽,但没有一个肽似乎是一种物种所特有的。因此,我们得出结论,对于 STH,没有一个肽被证明具有足够的敏感性或物种特异性。对于 S. mansoni,鉴定出了一些有前途的肽,这促使进一步研究。基于这些结果,线性表位不太可能在检测流行地区社区中针对 STH 的物种特异性抗体反应方面非常有用。对于 S. mansoni,微外显子基因 12(MEG-12)蛋白的一个特殊肽值得进一步研究。此外,这项研究强调了需要有特征明确的生物库来进行生物标志物发现,特别是当设想整合多个疾病项目时。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8358/8081252/90c4afb23bc8/pntd.0009369.g001.jpg

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