Motamedi Hamid, Shoja Saeed, Abbasi Maryam
Asadabad School of Medical Sciences, Asadabad, Iran.
Endocrinology and Metabolism Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
PLoS One. 2025 Feb 27;20(2):e0316699. doi: 10.1371/journal.pone.0316699. eCollection 2025.
Bacterial vaginosis (BV) is the most common vaginal dysbiosis in fertile women, which is associated with side effects including the risk of premature birth. Gardnerella vaginalis (G. vaginalis) is a facultative anaerobic bacillus known as the main pathogen responsible for BV. In this study, using bioinformatics and immunoinformatics methods, a multi-epitope vaccine with optimal population coverage against BV caused by G. vaginalis was designed.
Amino acid sequences of two important virulence factors (Vaginolysin and Sialidase) of G. vaginalis were retrieved from NCBI and UniProt databases. At first, three online servers ABCpred, BCPREDS and LBtope were used to predict linear B-cell epitopes (BCEs) and IEDB server was used for T cells. Then the antigenicity, toxicity, allergenicity were evaluated using bioinformatics tools. After modeling the three-dimensional (3D) structure of the vaccine by Robetta Server, molecular docking and molecular dynamics were performed. Finally, immune simulation and in silico cloning were considered effective for the design of vaccine production strategy.
In total, six epitopes of BCEs, eight epitopes from CD4+ and seven epitopes from CD8+ were selected. The designed multi-epitope vaccine was non-allergenic and non-toxic and showed high levels of antigenicity and immunogenicity. After the 3D structure was predicted, it was refined and validated, which resulted in an optimized model with a Z-score of -7.4. Molecular docking and molecular dynamics simulation of the designed vaccine revealed stable and strong binding interactions. Finally, the results of vaccine immunity simulation showed a significant increase in immunoglobulins, higher levels of IFN-γ and IL-2.
According to the findings, the candidate multi-epitope vaccine has stable structural features. It also has the potential to stimulate long-term immunity in the host, but wet-lab validation is needed to justify it.
细菌性阴道病（BV）是育龄妇女中最常见的阴道生态失调疾病，它与包括早产风险在内的副作用相关。阴道加德纳菌（G. vaginalis）是一种兼性厌氧杆菌，被认为是导致BV的主要病原体。在本研究中，运用生物信息学和免疫信息学方法，设计了一种针对由阴道加德纳菌引起的BV具有最佳人群覆盖率的多表位疫苗。
从NCBI和UniProt数据库中检索阴道加德纳菌两种重要毒力因子（阴道溶素和唾液酸酶）的氨基酸序列。首先，使用ABCpred、BCPREDS和LBtope这三个在线服务器预测线性B细胞表位（BCEs），并使用IEDB服务器预测T细胞表位。然后利用生物信息学工具评估抗原性、毒性和致敏性。通过Robetta服务器对疫苗的三维（3D）结构进行建模后，进行分子对接和分子动力学分析。最后，免疫模拟和计算机克隆被认为对疫苗生产策略的设计有效。
总共选择了6个BCEs表位、8个CD4 +表位和7个CD8 +表位。设计的多表位疫苗无致敏性和毒性，具有高水平的抗原性和免疫原性。预测3D结构后，对其进行了优化和验证，得到了一个Z值为-7.4的优化模型。设计疫苗的分子对接和分子动力学模拟显示出稳定且强烈的结合相互作用。最后，疫苗免疫模拟结果显示免疫球蛋白显著增加，IFN-γ和IL-2水平更高。
根据研究结果，候选多表位疫苗具有稳定的结构特征。它也有潜力在宿主体内刺激长期免疫，但需要进行湿实验室验证来证实这一点。
