Department of Medical Biotechnology, School of Paramedical, Gerash University of Medical Sciences, Gerash, Iran.
Endocrinology and Metabolism Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Sci Rep. 2024 Nov 16;14(1):28294. doi: 10.1038/s41598-024-79503-y.
Antibiotic resistance in bacterial pathogen infections is a growing global issue that occurs due to their adaptation to changing environmental conditions. Therefore, producing an efficient vaccine as an alternative approach can improve the immune system, eradicate related pathogens, and overcome this growing problem. Streptococcus agalactiae belongs to group B Streptococcus (GBS). Colonization of GBS during pregnancy is a significant risk factor for infants and young children. S. agalactiae infected population exhibits resistance to beta-lactams, including penicillin and the second-line antibiotics erythromycin and clindamycin. On the other hand, there are currently no commercial vaccines against this pathogen. Vaccination of pregnant women is a highly effective method to protect newborns and infants from S. agalactiae infection, and it has been identified as an urgent demand by the World Health Organization. This study employed various immunoinformatic tools to develop an effective vaccine that could trigger both humoral and cell-mediated immunity and prevent disease. For this purpose, three conserved antigenic proteins of the main pathogenic strains of S. agalactiae were utilized to predict CTL, HTL, and B-cell epitopes for producing an mRNA vaccine against different strains of S. agalactiae. The selected epitopes were fused using proper linkers. The Resuscitation promoting factor E (RpfE) sequence was incorporated in the designed vaccine construct as an adjuvant to boost its immune response. Different physicochemical characteristics of the final designed vaccine, modeling of the three-dimensional structure, molecular docking, molecular dynamics simulation, and immunological response simulation were screened following vaccine administration in an in vivo model. Computational immune simulation data identified that IgG1, IgM, INF γ, IL-2, T helper, and B-cell populations increased significantly after vaccination. These findings suggested that the vaccine candidate may provide good protection against S. agalactiae infection. However, experimental and animal model studies are required for additional validation and implementation in human vaccination programs.
细菌病原体感染中的抗生素耐药性是一个日益严重的全球问题，它是由于细菌适应不断变化的环境条件而产生的。因此，作为一种替代方法，生产有效的疫苗可以改善免疫系统，消除相关病原体，并克服这一日益严重的问题。无乳链球菌属于 B 群链球菌（GBS）。孕妇的 GBS 定植是婴儿和幼儿的一个重要危险因素。感染无乳链球菌的人群对包括青霉素在内的β-内酰胺类抗生素以及二线抗生素红霉素和克林霉素表现出耐药性。另一方面，目前还没有针对这种病原体的商业疫苗。对孕妇进行疫苗接种是保护新生儿和婴儿免受无乳链球菌感染的一种非常有效的方法，世界卫生组织已将其确定为一项紧迫需求。本研究采用了各种免疫信息学工具来开发一种有效的疫苗，以引发体液和细胞介导的免疫反应并预防疾病。为此，利用无乳链球菌主要致病株的三种保守抗原蛋白，预测 CTL、HTL 和 B 细胞表位，以生产针对不同无乳链球菌株的 mRNA 疫苗。选择的表位通过合适的接头融合。复苏促进因子 E（RpfE）序列被整合到设计的疫苗构建体中作为佐剂，以增强其免疫反应。在体内模型中接种疫苗后，对最终设计的疫苗的不同理化特性、三维结构建模、分子对接、分子动力学模拟和免疫反应模拟进行了筛选。计算免疫模拟数据表明，接种疫苗后 IgG1、IgM、INFγ、IL-2、T 辅助和 B 细胞群体显著增加。这些发现表明，候选疫苗可能为无乳链球菌感染提供良好的保护。然而，还需要进行实验和动物模型研究，以进一步验证并将其应用于人类疫苗接种计划。
