Kashyap Manju, Jaiswal Varun, Farooq Umar
Faculty of Applied Sciences and Biotechnology, Shoolini University, Himachal Pradesh, India.
Dept. of Bioinformatics, School of Electrical and Computer Science Engineering, Shoolini University, Solan, Himachal Pradesh, India.
Infect Genet Evol. 2017 Sep;53:107-115. doi: 10.1016/j.meegid.2017.05.022. Epub 2017 May 23.
Visceral leishmaniasis is a dreadful infectious disease and caused by the intracellular protozoan parasites, Leishmania donovani and Leishmania infantum. Despite extensive efforts for developing effective prophylactic vaccine, still no vaccine is available against leishmaniasis. However, advancement in immunoinformatics methods generated new dimension in peptide based vaccine development. The present study was aimed to identify T-cell epitopes from the vaccine candidate antigens like Lipophosphogylcan-3(LPG-3) and Nucleoside hydrolase (NH) from the L. donovani using in silico methods. Available best tools were used for the identification of promiscuous peptides for MHC class-II alleles. A total of 34 promiscuous peptides from LPG-3, 3 from NH were identified on the basis of their 100% binding affinity towards all six HLA alleles, taken in this study. These peptides were further checked computationally to know their IFN-γ and IL4 inducing potential and nine peptides were identified. Peptide binding interactions with predominant HLA alleles were done by docking. Out of nine docked promiscuous peptides, only two peptides (QESRILRVIKKKLVR, RILRVIKKKLVRKTL), from LPG-3 and one peptide (FDKFWCLVIDALKRI) from NH showed lowest binding energy with all six alleles. These promiscuous T-cell epitopes were predicted on the basis of their antigenicity, hydrophobicity, potential immune response and docking scores. The immunogenicity of predicted promiscuous peptides might be used for subunit vaccine development with immune-modulating adjuvants.
内脏利什曼病是一种可怕的传染病，由细胞内原生动物寄生虫杜氏利什曼原虫和婴儿利什曼原虫引起。尽管为开发有效的预防性疫苗付出了巨大努力，但仍然没有针对利什曼病的疫苗。然而，免疫信息学方法的进步为基于肽的疫苗开发带来了新的维度。本研究旨在使用计算机模拟方法从杜氏利什曼原虫的候选疫苗抗原如脂磷壁酸聚糖-3（LPG-3）和核苷水解酶（NH）中鉴定T细胞表位。使用可用的最佳工具来鉴定MHC-II类等位基因的混杂肽。基于本研究中所采用的对所有六个HLA等位基因的100%结合亲和力，从LPG-3中总共鉴定出34个混杂肽，从NH中鉴定出3个。进一步通过计算机检查这些肽以了解它们诱导IFN-γ和IL4的潜力，并鉴定出9个肽。通过对接进行肽与主要HLA等位基因的结合相互作用。在9个对接的混杂肽中，只有来自LPG-3的两个肽（QESRILRVIKKKLVR、RILRVIKKKLVRKTL）和来自NH的一个肽（FDKFWCLVIDALKRI）与所有六个等位基因显示出最低的结合能。这些混杂的T细胞表位是根据它们的抗原性、疏水性、潜在免疫反应和对接分数预测的。预测的混杂肽的免疫原性可用于与免疫调节佐剂一起开发亚单位疫苗。
