A bioinformatics tool for epitope-based vaccine design that accounts for human ethnic diversity: Application to emerging infectious diseases
A bioinformatics tool for epitope-based vaccine design that accounts for human ethnic diversity: Application to emerging infectious diseases
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DOI：
10.1016/j.vaccine.2015.01.040
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发表时间：
2015-03-03
期刊：
影响因子：
5.5
通讯作者：
Kobe, Bostjan
中科院分区：
文献类型：
--
作者：
Oyarzun, Patricio;Ellis, Jonathan J.;Kobe, Bostjan
背景：基于多个T细胞表位的肽疫苗接种可用于靶向明确定义的种族人群。由于对T细胞表位的应答受到HLA蛋白的限制，因此T细胞表位的HLA特异性成为基于表位的疫苗设计的主要考虑因素。我们以前已经表明，CD 4（+）T-细胞表位限制95%的人类MHC II类蛋白可以预测具有高特异性。方法：我们在这里描述的整合表位预测与人口覆盖率和表位选择算法。人口覆盖率评估使用等位基因频率网络数据库。我们提出了计算平台Predivac-2.0 HLA II类限制性表位为基础的疫苗设计，其中全面占人类遗传多样性。结果：我们验证了该工具的性能鉴定混杂和免疫显性CD 4 + T细胞表位从人类免疫缺陷病毒（HIV）蛋白Gag。我们进一步描述了一个应用程序的背景下，与拉沙，尼帕和亨德拉病毒相关的新兴传染病的表位为基础的疫苗设计。推定的CD 4 + T细胞表位被定位在这些病原体的表面糖蛋白上，并且是进行实验测试的良好候选者，因为它们具有在各自的目标人群中的疫苗接种设置中提供同源帮助的潜力。Predivac-2.0是一种基于表位的疫苗设计新方法，特别适合应用于病毒相关的新发传染病，因为病毒的地理分布已明确界定，需要接种疫苗的族裔群体也可确定（“面向族裔的办法”）。(C)2015爱思唯尔有限公司版权所有。
Background: Peptide vaccination based on multiple T-cell epitopes can be used to target well-defined ethnic populations. Because the response to T-cell epitopes is restricted by HLA proteins, the HLA specificity of T-cell epitopes becomes a major consideration for epitope-based vaccine design. We have previously shown that CD4(+) T-cell epitopes restricted by 95% of human MHC class II proteins can be predicted with high-specificity.Methods: We describe here the integration of epitope prediction with population coverage and epitope selection algorithms. The population coverage assessment makes use of the Allele Frequency Net Database. We present the computational platform Predivac-2.0 for HLA class II-restricted epitope-based vaccine design, which accounts comprehensively for human genetic diversity.Results: We validated the performance of the tool on the identification of promiscuous and immunodominant CD4+ T-cell epitopes from the human immunodeficiency virus (HIV) protein Gag. We further describe an application for epitope-based vaccine design in the context of emerging infectious diseases associated with Lassa, Nipah and Hendra viruses. Putative CD4+ T-cell epitopes were mapped on the surface glycoproteins of these pathogens and are good candidates to be experimentally tested, as they hold potential to provide cognate help in vaccination settings in their respective target populations.Conclusion: Predivac-2.0 is a novel approach in epitope-based vaccine design, particularly suited to be applied to virus-related emerging infectious diseases, because the geographic distributions of the viruses are well defined and ethnic populations in need of vaccination can be determined ("ethnicity-oriented approach"). (C) 2015 Elsevier Ltd. All rights reserved.