{"title":"通过反向疫苗学和基因组学方法确定新的候选组合疫苗,以控制肠道病原体。","authors":"Saeed Mikaeel, Abbas Doosti, Ali Sharifzadeh","doi":"10.1186/s12865-024-00626-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>The pathogenic microorganisms that cause intestinal diseases can significantly jeopardize people's health. Currently, there are no authorized treatments or vaccinations available to combat the germs responsible for intestinal disease.</p><p><strong>Methods: </strong>Using immunoinformatics, we developed a potent multi-epitope Combination (combo) vaccine versus Salmonella and enterohemorrhagic E. coli. The B and T cell epitopes were identified by performing a conservancy assessment, population coverage analysis, physicochemical attributes assessment, and secondary and tertiary structure assessment of the chosen antigenic polypeptide. The selection process for vaccine development included using several bioinformatics tools and approaches to finally choose two linear B-cell epitopes, five CTL epitopes, and two HTL epitopes.</p><p><strong>Results: </strong>The vaccine had strong immunogenicity, cytokine production, immunological properties, non-toxicity, non-allergenicity, stability, and potential efficacy against infections. Disulfide bonding, codon modification, and computational cloning were also used to enhance the stability and efficacy of expression in the host E. coli. The vaccine's structure has a strong affinity for the TLR4 ligand and is very durable, as shown by molecular docking and molecular modeling. The results of the immunological simulation demonstrated that both B and T cells had a heightened response to the vaccination component.</p><p><strong>Conclusions: </strong>The comprehensive in silico analysis reveals that the proposed vaccine will likely elicit a robust immune response against pathogenic bacteria that cause intestinal diseases. 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引用次数: 0
摘要
目的:导致肠道疾病的病原微生物会严重危害人们的健康。目前,还没有获得授权的治疗方法或疫苗来对抗导致肠道疾病的病菌:方法:利用免疫信息学,我们开发出了一种针对沙门氏菌和肠出血性大肠杆菌的强效多表位组合(combo)疫苗。通过对所选抗原多肽进行保守性评估、群体覆盖率分析、理化属性评估以及二级和三级结构评估,确定了B细胞和T细胞表位。疫苗开发的选择过程包括使用多种生物信息学工具和方法,最终选择了两个线性 B 细胞表位、五个 CTL 表位和两个 HTL 表位:结果:该疫苗具有很强的免疫原性、细胞因子产生能力、免疫学特性、无毒性、无致敏性、稳定性和潜在的抗感染功效。为了提高在宿主大肠杆菌中表达的稳定性和有效性,还采用了二硫键、密码子修饰和计算克隆等方法。分子对接和分子建模显示,该疫苗的结构与 TLR4 配体有很强的亲和力,而且非常持久。免疫学模拟结果表明,B 细胞和 T 细胞对疫苗成分的反应都有所增强:综合硅学分析表明,拟议的疫苗很可能会引起针对导致肠道疾病的致病菌的强大免疫反应。因此,它是一个值得进一步实验测试的有前途的选择。
Putative new combination vaccine candidates identified by reverse vaccinology and genomic approaches to control enteric pathogens.
Objectives: The pathogenic microorganisms that cause intestinal diseases can significantly jeopardize people's health. Currently, there are no authorized treatments or vaccinations available to combat the germs responsible for intestinal disease.
Methods: Using immunoinformatics, we developed a potent multi-epitope Combination (combo) vaccine versus Salmonella and enterohemorrhagic E. coli. The B and T cell epitopes were identified by performing a conservancy assessment, population coverage analysis, physicochemical attributes assessment, and secondary and tertiary structure assessment of the chosen antigenic polypeptide. The selection process for vaccine development included using several bioinformatics tools and approaches to finally choose two linear B-cell epitopes, five CTL epitopes, and two HTL epitopes.
Results: The vaccine had strong immunogenicity, cytokine production, immunological properties, non-toxicity, non-allergenicity, stability, and potential efficacy against infections. Disulfide bonding, codon modification, and computational cloning were also used to enhance the stability and efficacy of expression in the host E. coli. The vaccine's structure has a strong affinity for the TLR4 ligand and is very durable, as shown by molecular docking and molecular modeling. The results of the immunological simulation demonstrated that both B and T cells had a heightened response to the vaccination component.
Conclusions: The comprehensive in silico analysis reveals that the proposed vaccine will likely elicit a robust immune response against pathogenic bacteria that cause intestinal diseases. Therefore, it is a promising option for further experimental testing.
期刊介绍:
BMC Immunology is an open access journal publishing original peer-reviewed research articles in molecular, cellular, tissue-level, organismal, functional, and developmental aspects of the immune system as well as clinical studies and animal models of human diseases.