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基于计算方法设计用于动物锥虫病的表位疫苗组合

Design of an Epitope-Based Vaccine Ensemble for Animal Trypanosomiasis by Computational Methods.

作者信息

Michel-Todó Lucas, Bigey Pascal, Reche Pedro A, Pinazo María-Jesus, Gascón Joaquim, Alonso-Padilla Julio

机构信息

Barcelona Institute for Global Health (ISGlobal), Hospital Clínic - University of Barcelona, 08036 Barcelona, Spain.

Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Paris, UTCBS, F-75006 Paris, France.

出版信息

Vaccines (Basel). 2020 Mar 16;8(1):130. doi: 10.3390/vaccines8010130.

Abstract

African animal trypanosomiasis is caused by vector-transmitted parasites of the genus . and are predominant in Africa; and in America and Asia. They have in common an extracellular lifestyle and livestock tropism, which provokes huge economic losses in regions where vectors are endemic. There are licensed drugs to treat the infections, but adherence to treatment is poor and appearance of resistances common. Therefore, the availability of a prophylactic vaccine would represent a major breakthrough towards the management and control of the disease. Selection of the most appropriate antigens for its development is a bottleneck step, especially considering the limited resources allocated. Herein we propose a vaccine strategy based on multiple epitopes from multiple antigens to counteract the parasites´ biological complexity. Epitopes were identified by computer-assisted genome-wide screenings, considering sequence conservation criteria, antigens annotation and sub-cellular localization, high binding affinity to antigen presenting molecules, and lack of cross-reactivity to proteins in cattle and other breeding species. We ultimately provide 31 B-cell, 8 CD4 T-cell, and 15 CD8 T-cell epitope sequences from 30 distinct antigens for the prospective design of a genetic ensemble vaccine against the four trypanosome species responsible for African animal trypanosomiasis.

摘要

非洲动物锥虫病由属的媒介传播寄生虫引起。和在非洲占主导地位;和在美洲和亚洲占主导地位。它们的共同特点是细胞外生活方式和嗜家畜性,这在媒介流行的地区引发了巨大的经济损失。有许可药物治疗这些感染,但治疗依从性差且耐药性普遍出现。因此,预防性疫苗的可用性将是该疾病管理和控制方面的一项重大突破。为其开发选择最合适的抗原是一个瓶颈步骤,尤其是考虑到分配的资源有限。在此,我们提出一种基于多种抗原的多个表位的疫苗策略,以应对寄生虫的生物学复杂性。通过计算机辅助的全基因组筛选鉴定表位,考虑序列保守标准、抗原注释和亚细胞定位、与抗原呈递分子的高结合亲和力以及与牛和其他养殖物种中的蛋白质无交叉反应性。我们最终从30种不同抗原中提供了31个B细胞、8个CD4 T细胞和15个CD8 T细胞表位序列,用于针对导致非洲动物锥虫病的四种锥虫物种的基因组合疫苗的前瞻性设计。

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