Construction and validation of a novel multi-epitope in silico vaccine design against the paramyosin protein of Opisthorchis viverrini using immunoinformatics analyses
Alok Kafle , Jan Clyden B. Tenorio , Roshan Kumar Mahato , Sahara Dhakal , Muhammad F. Heikal , Sutas Suttiprapa
{"title":"Construction and validation of a novel multi-epitope in silico vaccine design against the paramyosin protein of Opisthorchis viverrini using immunoinformatics analyses","authors":"Alok Kafle , Jan Clyden B. Tenorio , Roshan Kumar Mahato , Sahara Dhakal , Muhammad F. Heikal , Sutas Suttiprapa","doi":"10.1016/j.actatropica.2024.107389","DOIUrl":null,"url":null,"abstract":"<div><p>Liver fluke infection caused by <em>Opisthorchis viverrini</em> (<em>O. viverrini</em>) remains a significant but neglected health threat across Southeastern Asia. The early infective anabolic growth stage of <em>O. viverrini</em> expresses and exposes proteins integral for the growth and maturation of immature worms to the adult catabolic stage. Among these proteins, paramyosin emerged as a distinct immunogenic protein during opisthorchiasis. The functional region of the paramyosin protein known as myosin tail was selected to design a multi-epitope vaccine (MEV) to elicit T and B cell immune responses in susceptible human hosts utilizing various immunoinformatics and <em>in silico</em> vaccinology tools. The vaccine candidate had several B- and T-cell epitopes that stimulate both humoral and cellular immune responses. Moreover, <em>in silico</em> structural, docking, and dynamic analyses showed that the construct interacted with target immune receptors effectively, which may result in sufficient immunological stimulation. Analysis of simulated coverage efficacy also supports vaccine application in the field. Cloning and expression of the vaccine candidate were determined to be viable based on physicochemical and <em>in silico</em> assessments. These results reveal that the vaccine candidate developed herein is stable and potentially useful in addressing opisthorchiasis. The promising result of this study establishes a strong platform for initiating laboratory and efficacy trials for the vaccine candidate.</p></div>","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":"260 ","pages":"Article 107389"},"PeriodicalIF":2.1000,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta tropica","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0001706X24002717","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PARASITOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Liver fluke infection caused by Opisthorchis viverrini (O. viverrini) remains a significant but neglected health threat across Southeastern Asia. The early infective anabolic growth stage of O. viverrini expresses and exposes proteins integral for the growth and maturation of immature worms to the adult catabolic stage. Among these proteins, paramyosin emerged as a distinct immunogenic protein during opisthorchiasis. The functional region of the paramyosin protein known as myosin tail was selected to design a multi-epitope vaccine (MEV) to elicit T and B cell immune responses in susceptible human hosts utilizing various immunoinformatics and in silico vaccinology tools. The vaccine candidate had several B- and T-cell epitopes that stimulate both humoral and cellular immune responses. Moreover, in silico structural, docking, and dynamic analyses showed that the construct interacted with target immune receptors effectively, which may result in sufficient immunological stimulation. Analysis of simulated coverage efficacy also supports vaccine application in the field. Cloning and expression of the vaccine candidate were determined to be viable based on physicochemical and in silico assessments. These results reveal that the vaccine candidate developed herein is stable and potentially useful in addressing opisthorchiasis. The promising result of this study establishes a strong platform for initiating laboratory and efficacy trials for the vaccine candidate.
由肝吸虫(Opisthorchis viverrini,O. viverrini)引起的肝吸虫感染仍然是整个东南亚地区一个重要的健康威胁,但却被忽视了。肝吸虫的早期感染性合成代谢生长阶段会表达和暴露未成熟蠕虫生长和成熟至成虫分解代谢阶段不可或缺的蛋白质。在这些蛋白中,副肌球蛋白(paramyosin)是乳鼠线虫病期间出现的一种独特的免疫原性蛋白。我们选择了副黏多糖蛋白的功能区--肌球蛋白尾部--来设计一种多表位疫苗(MEV),利用各种免疫信息学和硅学疫苗学工具,在易感人类宿主中激发 T 细胞和 B 细胞免疫反应。候选疫苗具有多个 B 细胞和 T 细胞表位,可激发体液免疫和细胞免疫反应。此外,硅学结构、对接和动态分析显示,该构建体能有效地与目标免疫受体相互作用,从而产生足够的免疫刺激。模拟覆盖效力分析也为疫苗在该领域的应用提供了支持。根据理化和硅学评估,确定候选疫苗的克隆和表达是可行的。这些结果表明,本研究开发的候选疫苗是稳定的,并有可能用于解决口蹄疫问题。这项研究的良好结果为启动候选疫苗的实验室和药效试验建立了一个强有力的平台。
期刊介绍:
Acta Tropica, is an international journal on infectious diseases that covers public health sciences and biomedical research with particular emphasis on topics relevant to human and animal health in the tropics and the subtropics.