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通过计算机预测鉴定布氏锥虫表达的新型保护性 VSG 抗原,并尝试使用 IL-12 作为佐剂设计高度免疫原性的 DNA 疫苗。

In silico identification of novel protective VSG antigens expressed by Trypanosoma brucei and an effort for designing a highly immunogenic DNA vaccine using IL-12 as adjuvant.

机构信息

Centre of Bioinformatics, School of Biotechnology, Shri Mata Vaishno Devi (SMVD) University, Jammu, J&K 182320, India.

出版信息

Microb Pathog. 2011 Jul-Aug;51(1-2):77-87. doi: 10.1016/j.micpath.2011.01.011. Epub 2011 Feb 22.

Abstract

African trypanosomiasis continues to be a major health problem, with more adults dying from this disease world-wide. As the sequence diversity of Trypanosoma brucei is extreme, with VSGs having 15-25% identity with most other VSGs, hence it displays a huge diversity of adaptations and host specificities. Therefore the need for an improved vaccine has become an international priority. The highly conserved and specific epitopes acting as both CD8+ and CD4+ T-cell epitopes (FLINKKPAL and FTALCTLAA) were predicted from large bunch of VSGs of T. brucei. Besides, some other potential epitopes with very high affinity for MHC I and II molecules were also determined while taking consideration on the most common HLA in the general population which accounts for major ethnicities. The vaccine candidates were found to be effective even for non-african populations as predicted by population coverage analysis. Hence the migrating travelers acting as a spread means of the infection can probably also be treated successfully after injection of such a multiepitopic vaccine. Exploiting the immunoinformatics approaches, we designed a potential vaccine by using the consensus epitopic sequence of 388 VSG proteins of T. brucei and performed in silico cloning of multiepitopic antigenic DNA sequence in pBI-CMV1 vector. Moreover, various techniques like codon adaptation, CpG optimization, removal of self recognized epitopes, use of adjuvant and co-injection with plasmids expressing immune-stimulatory molecules were implemented to enhance the immunogenicity of the proposed in silico vaccine.

摘要

非洲锥虫病仍然是一个主要的健康问题,全球有更多的成年人因此病死亡。由于布氏锥虫的序列多样性极高,VSGs 与大多数其他 VSGs 的同源性为 15-25%,因此它表现出极大的适应性和宿主特异性。因此,需要开发一种改良的疫苗已成为国际优先事项。从大量布氏锥虫的 VSG 中预测出高度保守且特异性的表位,这些表位既作为 CD8+和 CD4+ T 细胞表位,也作为 FLINKKPAL 和 FTALCTLAA。此外,还确定了一些其他具有高亲和力 MHC I 和 II 分子的潜在表位,同时考虑了普通人群中最常见的 HLA,这些 HLA 占主要种族。通过群体覆盖分析预测,候选疫苗对非非洲人群也有效。因此,作为感染传播手段的迁徙旅行者在接种这种多表位疫苗后也可能得到成功治疗。通过利用免疫信息学方法,我们使用布氏锥虫的 388 种 VSG 蛋白的共识表位序列设计了一种潜在的疫苗,并在 pBI-CMV1 载体中进行了多表位抗原 DNA 序列的计算机克隆。此外,还实施了各种技术,如密码子适应、CpG 优化、去除自身识别表位、使用佐剂以及与表达免疫刺激分子的质粒共注射,以增强计算机疫苗的免疫原性。

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