Felice Andrei Giacchetto, Rodrigues Thaís Cristina Vilela, Marques Pedro Henrique, Zen Felipe Lucas, Lemes Marcela Rezende, Trevisan Rafael Obata, Andrade Bruno Silva, de Oliveira Carlo José Freire, Azevedo Vasco Ariston de Carvalho, Tiwari Sandeep, Soares Siomar de Castro
Universidade Federal do Triângulo Mineiro, Instituto de Ciências Biológicas e Naturais, Programa de Pós-Graduação em Medicina Tropical e Infectologia, Uberaba, MG, Brasil.
Universidade Federal de Minas Gerais, Departamento de Genética, Ecologia e Evolução, Belo Horizonte, MG, Brasil.
Mem Inst Oswaldo Cruz. 2025 Mar 21;120:e240201. doi: 10.1590/0074-02760240201. eCollection 2025.
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.
Thus, this study aimed to develop an in silico multi-epitope vaccine against Rickettsia.
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.
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.
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.
立克次氏体是一类革兰氏阴性细菌，可引发多种疾病，包括流行性斑疹伤寒、落基山斑疹热和地中海斑疹热。蜱传播这些疾病，且常见于卫生条件差的发展中地区。因此，难以估计这些疾病的病例数量，这给创建预防和诊断机制带来了挑战。
因此，本研究旨在开发一种针对立克次氏体的计算机多表位疫苗。
先前通过反向疫苗学鉴定出8种蛋白质作为潜在疫苗候选物，并筛选与MHC I类和II类分子结合的表位。然后分析这些表位的抗原性、致敏性和毒性。将选定的表位与AAY和GPGPG序列肽以及一种已知佐剂（大肠杆菌不耐热肠毒素的B链）连接，形成嵌合多表位蛋白。预测该蛋白的三维结构，并针对Toll样受体4（TLR4）进行分子对接分析。最后，使用C-ImmSim工具模拟对该蛋白的免疫反应。
共形成26个免疫原性表位，构成多表位疫苗RGME-VAC/ATS-1。该疫苗显示出优异的免疫原性参数，预计对宿主无毒或无致敏性。它还显示出对免疫细胞的良好潜在刺激作用，倾向于产生记忆细胞并引发IFN-γ分泌。
计算机验证表明，我们的研究成功设计了一种针对立克次氏体的创新多表位疫苗，解决了该属细菌引起的疾病难以捉摸的性质所带来的挑战。我们为进一步的实验探索以及这些疾病的靶向预防和诊断策略的开发提供了有希望的潜力。
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