In silico construction of a multi-epitope vaccine (RGME-VAC/ATS-1) against the Rickettsia genus using immunoinformatics.

IF 2.5 4区医学 Q2 PARASITOLOGY

Memorias do Instituto Oswaldo Cruz Pub Date : 2025-03-21 eCollection Date: 2025-01-01 DOI:10.1590/0074-02760240201

Andrei Giacchetto Felice, Thaís Cristina Vilela Rodrigues, Pedro Henrique Marques, Felipe Lucas Zen, Marcela Rezende Lemes, Rafael Obata Trevisan, Bruno Silva Andrade, Carlo José Freire de Oliveira, Vasco Ariston de Carvalho Azevedo, Sandeep Tiwari, Siomar de Castro Soares

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引用次数: 0

Abstract

Background: Rickettsia is a genus of Gram-negative bacteria that causes various diseases, including epidemic typhus, Rocky Mountain spotted fever, and Mediterranean spotted fever. Ticks transmit these diseases and commonly found in developing regions with poor sanitation. As a result, it is difficult to estimate the number of these diseases cases, making it challenging to create prevention and diagnostic mechanisms.

Objectives: Thus, this study aimed to develop an in silico multi-epitope vaccine against Rickettsia.

Methods: Eight proteins were previously identified as potential vaccine candidates through reverse vaccinology and were screened for epitopes that bind to MHC class I and II molecules. The epitopes were then analysed for antigenicity, allergenicity, and toxicity. The selected epitopes were linked with AAY and GPGPG sequences peptide and a known adjuvant, the B-chain of Escherichia coli heat-labile enterotoxin, to form a chimeric multi-epitope protein. The protein's three-dimensional structure was predicted, and molecular docking analysis was performed against the toll-like receptor 4 (TLR4). Finally, the immune response to the protein was simulated using C-ImmSim tool.

Findings: A total of 26 immunogenic epitopes, formed the multi-epitope vaccine RGME-VAC/ATS-1. The vaccine showed excellent immunogenic parameters and was predicted to do not be toxic or allergenic to the host. It also showed good potential stimulation of immune cells, with a propensity to generate memory cells and elicit IFN-γ secretion.

Main conclusions: The in silico validations suggest that our study successfully designed an innovative multi-epitope vaccine against Rickettsia, addressing the challenges posed by the elusive nature of diseases caused by this genus. We provide a promising potential for further experimental exploration and the development of targeted prevention and diagnostic strategies for these diseases.

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利用免疫信息学技术构建立克次体多表位疫苗（RGME-VAC/ATS-1）。

背景：立克次体是一种革兰氏阴性菌属，可引起多种疾病，包括流行性斑疹伤寒、落基山斑疹热和地中海斑疹热。蜱虫传播这些疾病，常见于卫生条件差的发展中地区。因此，很难估计这些疾病病例的数量，因此很难建立预防和诊断机制。目的：本研究旨在研制一种抗立克次体的多表位硅疫苗。方法：之前通过反向疫苗学鉴定了8种蛋白质作为潜在的候选疫苗，并筛选了与MHC I类和II类分子结合的表位。然后分析表位的抗原性、过敏原性和毒性。选择的表位与AAY和GPGPG序列肽以及已知的佐剂大肠杆菌热不稳定肠毒素b链连接，形成一个嵌合的多表位蛋白。预测了该蛋白的三维结构，并与toll样受体4 （TLR4）进行了分子对接分析。最后，使用C-ImmSim工具模拟对该蛋白的免疫反应。结果：共有26个免疫原性表位，形成了多表位疫苗RGME-VAC/ATS-1。该疫苗显示出良好的免疫原性参数，预计不会对宿主有毒或致敏。它还显示出良好的潜在刺激免疫细胞，倾向于产生记忆细胞和诱导IFN-γ分泌。主要结论：计算机验证表明，我们的研究成功设计了一种针对立克次体的创新多表位疫苗，解决了由立克次体引起的疾病难以捉摸的性质所带来的挑战。我们为这些疾病的进一步实验探索和有针对性的预防和诊断策略的发展提供了有希望的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Memorias do Instituto Oswaldo Cruz 医学-寄生虫学

CiteScore

5.00

自引率

3.60%

发文量

审稿时长

3-8 weeks

期刊介绍： Memórias do Instituto Oswaldo Cruz is a journal specialized in microbes & their vectors causing human infections. This means that we accept manuscripts covering multidisciplinary approaches and findings in the basic aspects of infectious diseases, e.g. basic in research in prokariotes, eukaryotes, and/or virus. Articles must clearly show what is the main question to be answered, the hypothesis raised, and the contribution given by the study. Priority is given to manuscripts reporting novel mechanisms and general findings concerning the biology of human infectious prokariotes, eukariotes or virus. Papers reporting innovative methods for diagnostics or that advance the basic research with these infectious agents are also welcome. It is important to mention what we do not publish: veterinary infectious agents research, taxonomic analysis and re-description of species, epidemiological studies or surveys or case reports and data re-analysis. Manuscripts that fall in these cases or that are considered of low priority by the journal editorial board, will be returned to the author(s) for submission to another journal.