Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Lucknow, 226028, India.
Molecular and Human Genetics Lab, Department of Zoology, University of Lucknow, Lucknow, 226007, India.
Comput Biol Chem. 2020 Jun;86:107259. doi: 10.1016/j.compbiolchem.2020.107259. Epub 2020 Apr 14.
Visceral leishmaniasis (VL) caused by Leishmania donovani is a fatal parasitic disease affecting primarily the poor population in endemic countries. Increasing number of deaths as well as resistant to existing drugs necessitates the development of an effective vaccine for successful treatment of VL. The present study employed a combinatorial approach for designing monomer vaccine construct against L. donovani by applying forecasted B- and T- cell epitopes from 4 genome derived antigenic proteins having secretory signal peptides and glycophosphatidylinositol (GPI) anchors with ≤ 1 transmembrane helix. The forecasted population coverage of chosen T cell epitope ensemble (combined HLA class I and II) cover 99.14 % of world-wide human population. The predicted 3D structure of vaccine constructs (VC1/VC2) were modeled using homology modeling approach and docked to innate immune receptors TLR-2 and TLR-4 with respective docking energies -1231.4/-910.3 and -1119.4/-1476 kcal/mol. Overall, the aforementioned designed vaccine constructs were found appropriate for including in self-assembly protein nanoparticles (SAPN) for further study in developing cutting-edge precision vaccine against VL in short duration with cost-effective manner.
内脏利什曼病（VL）由利什曼原虫引起，是一种致命的寄生虫病，主要影响流行国家的贫困人口。由于死亡人数的增加以及对现有药物的耐药性，需要开发一种有效的疫苗来成功治疗 VL。本研究采用组合方法，通过应用具有≤1 个跨膜螺旋的 4 种源自基因组的抗原蛋白的预测 B 细胞和 T 细胞表位，设计针对 L. donovani 的单体疫苗构建体。选择的 T 细胞表位集合（组合 HLA I 类和 II 类）的预测人群覆盖率涵盖了全球 99.14%的人类人口。使用同源建模方法对疫苗构建体（VC1/VC2）的预测 3D 结构进行建模，并与先天免疫受体 TLR-2 和 TLR-4 对接，各自的对接能为-1231.4/-910.3 和-1119.4/-1476 kcal/mol。总体而言，上述设计的疫苗构建体适合包含在自组装蛋白纳米颗粒（SAPN）中，以便在短时间内以具有成本效益的方式开发针对 VL 的尖端精准疫苗。
