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通过利用反向疫苗学和进化信息对[具体对象]进行全基因组扫描以寻找潜在的CD4 + T细胞疫苗候选物。

Genome-wide scan for potential CD4+ T-cell vaccine candidates in by exploiting reverse vaccinology and evolutionary information.

作者信息

Gupta Shishir K, Osmanoglu Özge, Minocha Rashmi, Bandi Sourish Reddy, Bencurova Elena, Srivastava Mugdha, Dandekar Thomas

机构信息

Department of Bioinformatics, Biocenter, Functional Genomics and Systems Biology Group, University of Würzburg, Würzburg, Germany.

Evolutionary Genomics Group, Center for Computational and Theoretical Biology, University of Würzburg, Würzburg, Germany.

出版信息

Front Med (Lausanne). 2022 Nov 3;9:1008527. doi: 10.3389/fmed.2022.1008527. eCollection 2022.

Abstract

is a globally emerging fungal pathogen responsible for causing nosocomial outbreaks in healthcare associated settings. It is known to cause infection in all age groups and exhibits multi-drug resistance with high potential for horizontal transmission. Because of this reason combined with limited therapeutic choices available, infection has been acknowledged as a potential risk for causing a future pandemic, and thus seeking a promising strategy for its treatment is imperative. Here, we combined evolutionary information with reverse vaccinology approach to identify novel epitopes for vaccine design that could elicit CD4+ T-cell responses against To this end, we extensively scanned the family of proteins encoded by genome. In addition, a pathogen may acquire substitutions in epitopes over a period of time which could cause its escape from the immune response thus rendering the vaccine ineffective. To lower this possibility in our design, we eliminated all rapidly evolving genes of with positive selection. We further employed highly conserved regions of multiple strains and identified two immunogenic and antigenic T-cell epitopes that could generate the most effective immune response against The antigenicity scores of our predicted vaccine candidates were calculated as 0.85 and 1.88 where 0.5 is the threshold for prediction of fungal antigenic sequences. Based on our results, we conclude that our vaccine candidates have the potential to be successfully employed for the treatment of infection. However, experiments are imperative to further demonstrate the efficacy of our design.

摘要

是一种在全球范围内出现的真菌病原体,可在医疗相关环境中引发医院感染暴发。已知它可导致所有年龄组感染,并表现出多重耐药性,具有高水平传播的潜力。由于这个原因,再加上可用的治疗选择有限,该感染已被认为是引发未来大流行的潜在风险,因此寻求一种有前景的治疗策略势在必行。在此,我们将进化信息与反向疫苗学方法相结合,以识别可引发针对的CD4 + T细胞反应的新型疫苗设计表位。为此,我们广泛扫描了基因组编码的蛋白质家族。此外,病原体可能会在一段时间内获得表位替换,这可能导致其逃避免疫反应,从而使疫苗无效。为了在我们的设计中降低这种可能性,我们消除了所有具有正选择的快速进化基因。我们进一步利用多个菌株的高度保守区域,鉴定出两个免疫原性和抗原性T细胞表位,它们可以产生针对的最有效免疫反应。我们预测的候选疫苗的抗原性得分计算为0.85和1.88,其中0.5是预测真菌抗原序列的阈值。根据我们的结果,我们得出结论,我们的候选疫苗有可能成功用于治疗感染。然而,必须进行实验以进一步证明我们设计的有效性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83c0/9669072/a5fd569f12e5/fmed-09-1008527-g001.jpg

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