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基于反向疫苗学和免疫信息学方法设计的一种针对霍乱和弧菌病的多表位疫苗(vme-VAC/MST-1)

Design of a multi-epitope vaccine (vme-VAC/MST-1) against cholera and vibriosis based on reverse vaccinology and immunoinformatics approaches.

作者信息

Marques Pedro Henrique, Rodrigues Thais Cristina Vilela, Santos Eduardo Horta, Bleicher Lucas, Aburjaile Flavia Figueira, Martins Flaviano S, Oliveira Carlo Jose Freire, Azevedo Vasco, Tiwari Sandeep, Soares Siomar

机构信息

Institute of Biological Sciences, Post-graduate Interunits Program in Bioinformatics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.

Department of Preventive Veterinary Medicine, School of Veterinary Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.

出版信息

J Biomol Struct Dyn. 2025 Mar;43(4):1788-1803. doi: 10.1080/07391102.2023.2293256. Epub 2023 Dec 19.

DOI:10.1080/07391102.2023.2293256
PMID:38112302
Abstract

Vibriosis and cholera are serious diseases distributed worldwide and caused by six marine bacteria of the 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 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 spp. However, further experimental analyses are required to measure the vaccine's effects Communicated by Ramaswamy H. Sarma.

摘要

弧菌病和霍乱是分布于全球的严重疾病,由该属的六种海洋细菌引起。每年有数千人死于这些疾病,因此需要开发新的预防措施。目前,现有的霍乱疫苗显示出约60%的有效性。在此,我们描述一种新的多表位疫苗“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。该疫苗旨在通过纳入针对细胞毒性T淋巴细胞(CTL)、辅助性T淋巴细胞(HTL)和B细胞预测的表位来对抗弧菌病和霍乱。这些表位是从通过消减基因组学、结合反向疫苗学揭示的六个疫苗靶点中鉴定出来的,并基于其预测的免疫原性使用免疫信息学方法进一步筛选。为构建该疫苗,将28个表位(24个CTL/B和4个HTL/B)与霍乱毒素B亚基的序列相连。佐剂分析表明,所得免疫原稳定、可溶、无毒且无致敏性。此外,它与宿主无同源性,并表现出强大的引发固有免疫、B细胞免疫和T细胞免疫反应的能力。我们的分析表明,它可能引发通过Toll样受体5(TLR5)途径介导的免疫反应,疫苗与受体的分子对接证明了这一点,对接显示出高亲和力和良好的反应。因此,预计vme-VAC/MST-1是针对致病性弧菌的一种安全有效的解决方案。然而,需要进一步的实验分析来衡量该疫苗的效果。由拉马斯瓦米·H·萨尔马传达。

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