Pedro Henrique Marques, Thais Cristina Vilela Rodrigues, Eduardo Horta Santos, Lucas Bleicher, Flavia Figueira Aburjaile, Flaviano S Martins, Carlo Jose Freire Oliveira, Vasco Azevedo, Sandeep Tiwari, Siomar Soares
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引用次数: 0
摘要
弧菌病和霍乱是分布于世界各地的严重疾病,由六种海洋弧菌引起。每年有数千人死于这些疾病,因此有必要开发新的预防措施。目前,现有霍乱疫苗的有效率约为 60%。我们在此介绍一种新型多表位疫苗 "vme-VAC/MST-1",它基于反向疫苗学确定的疫苗靶点和免疫信息学预测的表位,这两种方法是目前预测细菌病原体新疫苗的有效工具。该疫苗的设计目的是通过加入针对 CTL、HTL 和 B 细胞预测的表位来对抗弧菌病和霍乱。这些表位是从减法基因组学结合反向疫苗学揭示的六个疫苗靶点中确定的,并根据其预测的免疫原性使用免疫信息学方法进行了进一步筛选。为了构建疫苗,将 28 个表位(24 个 CTL/B 和 4 个 HTL/B)与霍乱毒素 B 亚基佐剂的序列连接起来。硅学分析表明,由此产生的免疫原稳定、可溶、无毒、无致敏性。此外,它与宿主没有同源性,并显示出诱发先天、B 细胞和 T 细胞免疫反应的强大能力。我们的分析表明,它很可能通过 TLR5 途径引起免疫反应,疫苗与该受体的分子对接证明了这一点,该对接显示了高亲和力和良好的反应。因此,vme-VAC/MST-1 被认为是针对致病性弧菌的一种安全有效的解决方案。 然而,还需要进一步的实验分析来衡量该疫苗在体内的效果。
Design of a multi-epitope vaccine (vme-VAC/MST-1) against cholera and vibriosis based on reverse vaccinology and immunoinformatics approaches.
Vibriosis and cholera are serious diseases distributed worldwide and caused by six marine bacteria of the Vibrio genus. Thousands of deaths occur each year due to these illnesses, necessitating the development of new preventive measures. Presently, the existing cholera vaccine demonstrates an effectiveness of approximately 60%. Here we describe a new multi-epitope vaccine, 'vme-VAC/MST-1' based on vaccine targets identified by reverse vaccinology and epitopes predicted by immunoinformatics, two currently effective tools for predicting new vaccines for bacterial pathogens. The vaccine was designed to combat vibriosis and cholera by incorporating epitopes predicted for CTL, HTL, and B cells. These epitopes were identified from six vaccine targets revealed through subtractive genomics, combined with reverse vaccinology, and were further filtered using immunoinformatics approaches based on their predicted immunogenicity. To construct the vaccine, 28 epitopes (24 CTL/B and 4 HTL/B) were linked to the sequence of the cholera toxin B subunit adjuvant. In silico analyses indicate that the resulting immunogen is stable, soluble, non-toxic, and non-allergenic. Furthermore, it exhibits no homology to the host and demonstrates a strong capacity to elicit innate, B-cell, and T-cell immune responses. Our analysis suggests that it is likely to elicit immune reactions mediated through the TLR5 pathway, as evidenced by the molecular docking of the vaccine with the receptor, which revealed high affinity and a favorable reaction. Thus, vme-VAC/MST-1 is predicted to be a safe and effective solution against pathogenic Vibrio spp. However, further experimental analyses are required to measure the vaccine's effects In vivo.Communicated by Ramaswamy H. Sarma.
期刊介绍:
The Journal of Biomolecular Structure and Dynamics welcomes manuscripts on biological structure, dynamics, interactions and expression. The Journal is one of the leading publications in high end computational science, atomic structural biology, bioinformatics, virtual drug design, genomics and biological networks.