Genome-wide prediction of vaccine targets for human herpes simplex viruses using Vaxign reverse vaccinology.
Genome-wide prediction of vaccine targets for human herpes simplex viruses using Vaxign reverse vaccinology.
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DOI：
10.1186/1471-2105-14-s4-s2
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发表时间：
2013
影响因子：
3
通讯作者：
He Y
中科院分区：
文献类型：
--
作者：
Xiang Z;He Y
单纯疱疹病毒 (HSV) 1 型和 2 型（HSV-1 和 HSV-2）是人类最常见的传染源。尚未获得安全有效的 HSV 疫苗许可。反向疫苗学是一种新兴的革命性疫苗开发策略，它首先通过基因组序列的信息学分析来预测疫苗靶标。 Vaxign (http://www.violinet.org/vaxign) 是第一个基于反向疫苗学的网络疫苗设计程序。在本研究中，我们使用 Vaxign 分析了 52 个疱疹病毒基因组，包括 3 个 HSV-1 基因组、1 个 HSV-2 基因组、8 个其他人类疱疹病毒基因组和 40 个非人类疱疹病毒基因组。含有77个蛋白质的HSV-1毒株17基因组被用作种子基因组。这 77 个蛋白质在另外两种 HSV-1 毒株（毒株 F 和毒株 H129）中是保守的。两种包膜糖蛋白 gJ 和 gG 在 HSV-2 或 8 种其他人类疱疹病毒中没有直系同源物。 7 种 HSV-1 蛋白（包括 gJ 和 gG）在所有 40 种非人类疱疹病毒中都没有直向同源物。所有人类疱疹病毒中有 19 种蛋白质是保守的，包括衣壳支架蛋白 UL26.5 (NP_044628.1)。作为唯一被预测为粘附素的 HSV-1 蛋白，UL26.5 是一个有前途的疫苗靶标。 MHC I 类和 II 类表位由 Vaxign Vaxitop 预测程序和最近安装并合并到 Vaxign 中的 IEDB 预测程序进行预测。我们的比较分析发现，这两个程序识别出基本相同的顶级表位，但一个程序预测的一些阳性结果可能与另一个程序预测的结果不同。总体而言，我们的 Vaxign 计算预测为合理的 HSV 疫苗开发提供了许多有希望的候选疫苗。该方法具有通用性，也可用于预测其他病毒疫苗靶标。
Herpes simplex virus (HSV) types 1 and 2 (HSV-1 and HSV-2) are the most common infectious agents of humans. No safe and effective HSV vaccines have been licensed. Reverse vaccinology is an emerging and revolutionary vaccine development strategy that starts with the prediction of vaccine targets by informatics analysis of genome sequences. Vaxign (http://www.violinet.org/vaxign) is the first web-based vaccine design program based on reverse vaccinology. In this study, we used Vaxign to analyze 52 herpesvirus genomes, including 3 HSV-1 genomes, one HSV-2 genome, 8 other human herpesvirus genomes, and 40 non-human herpesvirus genomes. The HSV-1 strain 17 genome that contains 77 proteins was used as the seed genome. These 77 proteins are conserved in two other HSV-1 strains (strain F and strain H129). Two envelope glycoproteins gJ and gG do not have orthologs in HSV-2 or 8 other human herpesviruses. Seven HSV-1 proteins (including gJ and gG) do not have orthologs in all 40 non-human herpesviruses. Nineteen proteins are conserved in all human herpesviruses, including capsid scaffold protein UL26.5 (NP_044628.1). As the only HSV-1 protein predicted to be an adhesin, UL26.5 is a promising vaccine target. The MHC Class I and II epitopes were predicted by the Vaxign Vaxitop prediction program and IEDB prediction programs recently installed and incorporated in Vaxign. Our comparative analysis found that the two programs identified largely the same top epitopes but also some positive results predicted from one program might not be positive from another program. Overall, our Vaxign computational prediction provides many promising candidates for rational HSV vaccine development. The method is generic and can also be used to predict other viral vaccine targets.