Banesh Sooram, Gupta Neharika, Reddy Chethireddy Vihadhar, Mallikarjunachari Uppuladinne, Patil Nupoor, Uddhavesh Sonavane, Saudagar Prakash
Department of Biotechnology, National Institute of Technology-Warangal, Warangal, 506004, Telangana, India.
High Performance Computing - Medical and Bioinformatics Applications, Centre for Development of Advanced Computing (C-DAC), Pune, Maharastra, India.
Heliyon. 2024 May 17;10(10):e31306. doi: 10.1016/j.heliyon.2024.e31306. eCollection 2024 May 30.
Leishmaniasis is a major infectious disease having high mortality which could be attributed to lack of a suitable vaccine candidate. We propose a novel approach to design multiepitope vaccine to leishmaniasis exploiting specific membrane proteome from infected macrophage from host. The MHC-I, MHC-II and BC epitopes predicted for unique proteins from the infected macrophages and and a MEV designed in various combinations (1a-1m). The epitope arrangements 1a, 1k, 1l, and 1 m showed a strong antigenicity profile and immune response. The molecular dynamics simulation indicate the 1k, 1l, and 1 m constructs have strong affinity toward TLR-2, TLR-3, and TLR-4. Overall the structural and immunogenicity profile suggests 1k is top candidate. Further, a computational model system with TLR-2, TLR-3, TLR-4, BCR, MHC-I and MHC-II was generated for 1k construct to understand the MEV interactions with immune components. Dihedral distribution and distance was enumerated to understand the movement of immune components towards 1k. The results indicate 1k has strong affinity for the immune response molecules especially TLR-3, BCR and MHC-II are coming in close contact with the MEV through the simulation. The study suggests that designed multi-epitope vaccine 1k has potential to induce proper immune response but warrants further studies.
利什曼病是一种死亡率很高的主要传染病，这可能归因于缺乏合适的候选疫苗。我们提出了一种新方法，利用宿主受感染巨噬细胞的特定膜蛋白质组来设计针对利什曼病的多表位疫苗。预测了来自受感染巨噬细胞独特蛋白质的MHC-I、MHC-II和BC表位，并以各种组合（1a-1m）设计了一种多表位疫苗（MEV）。表位排列1a、1k、1l和1m显示出很强的抗原性特征和免疫反应。分子动力学模拟表明，1k、1l和1m构建体对TLR-2、TLR-3和TLR-4具有很强的亲和力。总体而言，结构和免疫原性特征表明1k是最佳候选者。此外，为1k构建体生成了一个包含TLR-2、TLR-3、TLR-4、BCR、MHC-I和MHC-II的计算模型系统，以了解多表位疫苗与免疫成分的相互作用。列举了二面角分布和距离，以了解免疫成分向1k的移动。结果表明，1k对免疫反应分子具有很强的亲和力，特别是通过模拟发现TLR-3、BCR和MHC-II与多表位疫苗紧密接触。该研究表明，设计的多表位疫苗1k有潜力诱导适当的免疫反应，但需要进一步研究。
