Pandya Nirali, Kumar Amit
Department of Chemistry, National University of Singapore, Singapore, Singapore.
Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore, Madhya Pradesh, India.
J Biomol Struct Dyn. 2023;41(23):13563-13579. doi: 10.1080/07391102.2023.2175373. Epub 2023 Feb 10.
Cryptosporidium hominis, an anthropologically transferred species in the Cryptosporidium genus, represents many clinical studies in several countries. Its growth in the recent decade is primarily owing to epidemiologic studies. This parasite has complicated life cycles that require differentiation through a variety of phases of development and passage across two or more hosts throughout their lifetimes. As they move from host to host and environment to environment, pathogenic organisms are continually exposed to unexpected changes in the circumstances under which they develop. Heat shock proteins (HSPs) are targets of the host immune response; they are involved in the progression of diseases and play a significant part in this process. It has been discovered that the immunodominant immunogenic antigens in parasite infections HSPs. In this study, we have generated a multi-epitope vaccine against (C. hominis) by using heat shock proteins. The epitopes that were selected had a substantial binding affinity for the B- and T-cell reference set of alleles, a high antigenicity score, a nature that was not allergic, a high solubility, non-toxicity and good binders. The epitopes were incorporated into a chimeric vaccine by using appropriate linkers. In order to increase the immunogenicity of the connected epitopes and effectively activate both innate and adaptive immunity, an adjuvant was attached to the epitopes. We have also analyzed the physiochemical characteristics of the vaccine which were satisfactory and then lead to the development of a 3D model. In addition, the binding confirmation of the vaccine to the TLR-4 innate immune receptor was also determined using molecular docking and molecular dynamics (MD) simulation. The results of this simulation show that the vaccine has a strong binding affinity for TLR4, which indicates that the vaccine is highly effective. In general, the vaccine that has been described here has a good potential for inducing protective and targeted immunogenicity, however, this hypothesis is contingent upon more experimental testing.Communicated by Ramaswamy H. Sarma.
人隐孢子虫是隐孢子虫属中一种通过人传播的物种，在多个国家开展了许多临床研究。其在近十年中的增长主要归因于流行病学研究。这种寄生虫具有复杂的生命周期，需要在其整个生命周期中经历多个发育阶段并在两个或更多宿主之间传播才能完成分化。当它们在宿主与宿主之间以及环境与环境之间移动时，致病生物不断面临其发育环境中意想不到的变化。热休克蛋白（HSPs）是宿主免疫反应的靶点；它们参与疾病的发展过程并在这一过程中发挥重要作用。已发现寄生虫感染中的免疫显性免疫原性抗原为热休克蛋白。在本研究中，我们利用热休克蛋白制备了一种针对人隐孢子虫的多表位疫苗。所选择的表位对B细胞和T细胞等位基因参考集具有显著的结合亲和力、高抗原性评分、无过敏性质、高溶解度、无毒性且是良好的结合剂。通过使用合适的连接子将这些表位整合到嵌合疫苗中。为了增强连接表位的免疫原性并有效激活先天免疫和适应性免疫，在表位上连接了佐剂。我们还分析了该疫苗令人满意的理化特性，随后构建了三维模型。此外，还利用分子对接和分子动力学（MD）模拟确定了该疫苗与TLR-4先天免疫受体的结合情况。模拟结果表明该疫苗对TLR4具有很强的结合亲和力，这表明该疫苗非常有效。总体而言，本文所述的疫苗具有诱导保护性和靶向免疫原性良好潜力，然而，这一假设仍有待更多实验验证。由拉马斯瓦米·H·萨尔马通讯。
