Vilela Rodrigues Thaís Cristina, Jaiswal Arun Kumar, Lemes Marcela Rezende, da Silva Marcos Vinícius, Sales-Campos Helioswilton, Alcântara Luiz Carlos Júnior, Tosta Sthephane Fraga de Oliveira, Kato Rodrigo Bentes, Alzahrani Khalid J, Barh Debmalya, Azevedo Vasco Ariston de Carvalho, Tiwari Sandeep, Soares Siomar de Castro
Programa PG Em Bioinformática, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Department of Immunology, Microbiology and Parasitology, Institute of Biological Science and Natural Sciences, Federal University of Triângulo Mineiro (UFTM), Uberaba, 38025-180, MG, Brazil.
Comput Biol Med. 2022 Mar;142:105194. doi: 10.1016/j.compbiomed.2021.105194. Epub 2021 Dec 31.
Pneumonia is a serious global health problem that accounts for over one million deaths annually. Among the main microorganisms causing pneumonia, Mycoplasma pneumoniae is one of the most common ones for which a vaccine is immediately required. In this context, a multi-epitope vaccine against this pathogen could be the best option that can induce effective immune response avoiding any serious adverse reactions. In this study, using an immunoinformatics approach we have designed a multi-epitope vaccine (mpme-VAC/STV-1) against M. pneumoniae. Our designed mpme-VAC/STV-1 is constructed using CTL (cytotoxic T lymphocyte), HTL (Helper T lymphocyte), and B-cell epitopes. These epitopes are selected from the core proteins of 88 M. pneumoniae genomes that were previously identified through reverse vaccinology approaches. The epitopes were filtered according to their immunogenicity, population coverage, and several other criteria. Sixteen CTL/B- and thirteen HTL/B- epitopes that belong to 5 core proteins were combined together through peptide linkers to develop the mpme-VAC/STV-1. The heat-labile enterotoxin from E. coli was used as an adjuvant. The designed mpme-VAC/STV-1 is predicted to be stable, non-toxic, non-allergenic, non-host homologous, and with required antigenic and immunogenic properties. Docking and molecular dynamic simulation of mpme-VAC/STV-1 shows that it can stimulate TLR2 pathway mediated immunogenic reactions. In silico cloning of mpme-VAC/STV-1 in an expression vector also shows positive results. Finally, the mpme-VAC/STV-1 also shows promising efficacy in immune simulation tests. Therefore, our constructed mpme-VAC/STV-1 could be a safe and effective multi-epitope vaccine for immunization against pneumonia. However, it requires further experimental and clinical validations.
肺炎是一个严重的全球健康问题,每年导致超过100万人死亡。在引起肺炎的主要微生物中,肺炎支原体是最常见的需要立即研发疫苗的病原体之一。在这种情况下,针对这种病原体的多表位疫苗可能是诱导有效免疫反应并避免任何严重不良反应的最佳选择。在本研究中,我们采用免疫信息学方法设计了一种针对肺炎支原体的多表位疫苗(mpme-VAC/STV-1)。我们设计的mpme-VAC/STV-1是利用细胞毒性T淋巴细胞(CTL)、辅助性T淋巴细胞(HTL)和B细胞表位构建的。这些表位是从88个肺炎支原体基因组的核心蛋白中筛选出来的,这些基因组先前是通过反向疫苗学方法鉴定的。根据它们的免疫原性、人群覆盖率和其他几个标准对表位进行了筛选。属于5种核心蛋白的16个CTL/B表位和13个HTL/B表位通过肽接头连接在一起,以开发mpme-VAC/STV-1。来自大肠杆菌的热不稳定肠毒素用作佐剂。设计的mpme-VAC/STV-1预计是稳定的、无毒的、无过敏的、与宿主无同源性的,并且具有所需的抗原性和免疫原性。mpme-VAC/STV-1的对接和分子动力学模拟表明,它可以刺激TLR2途径介导的免疫反应。mpme-VAC/STV-1在表达载体中的电子克隆也显示出阳性结果。最后,mpme-VAC/STV-1在免疫模拟试验中也显示出有前景的疗效。因此,我们构建的mpme-VAC/STV-1可能是一种安全有效的用于预防肺炎的多表位疫苗。然而,它需要进一步的实验和临床验证。