Infection Control Center, Xiangya Hospital, Central South University, Changsha, China.
Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, China.
Front Immunol. 2022 May 26;13:887061. doi: 10.3389/fimmu.2022.887061. eCollection 2022.
is an exclusively anaerobic, spore-forming, and Gram-positive pathogen that is the most common cause of nosocomial diarrhea and is becoming increasingly prevalent in the community. Because is strictly anaerobic, spores that can survive for months in the external environment contribute to the persistence and diffusion of within the healthcare environment and community. Antimicrobial therapy disrupts the natural intestinal flora, allowing spores to develop into propagules that colonize the colon and produce toxins, thus leading to antibiotic-associated diarrhea and pseudomembranous enteritis. However, there is no licensed vaccine to prevent infection (CDI). In this study, a multi-epitope vaccine was designed using modern computer methods. Two target proteins, CdeC, affecting spore germination, and fliD, affecting propagule colonization, were chosen to construct the vaccine so that it could simultaneously induce the immune response against two different forms (spore and propagule) of . We obtained the protein sequences from the National Center for Biotechnology Information (NCBI) database. After the layers of filtration, 5 cytotoxic T-cell lymphocyte (CTL) epitopes, 5 helper T lymphocyte (HTL) epitopes, and 7 B-cell linear epitopes were finally selected for vaccine construction. Then, to enhance the immunogenicity of the designed vaccine, an adjuvant was added to construct the vaccine. The Prabi and RaptorX servers were used to predict the vaccine's two- and three-dimensional (3D) structures, respectively. Additionally, we refined and validated the structures of the vaccine construct. Molecular docking and molecular dynamics (MD) simulation were performed to check the interaction model of the vaccine-Toll-like receptor (TLR) complexes, vaccine-major histocompatibility complex (MHC) complexes, and vaccine-B-cell receptor (BCR) complex. Furthermore, immune stimulation, population coverage, and molecular cloning were also conducted. The foregoing findings suggest that the final formulated vaccine is promising against the pathogen, but more researchers are needed to verify it.
艰难梭菌是一种专性厌氧、产芽孢、革兰氏阳性病原体，是医院获得性腹泻的最常见原因，并且在社区中越来越普遍。由于艰难梭菌是严格的厌氧菌，因此能够在外部环境中存活数月的芽孢有助于在医疗保健环境和社区中保持和扩散艰难梭菌。抗生素治疗会破坏天然肠道菌群，使孢子发育成定居在结肠并产生毒素的繁殖体，从而导致抗生素相关性腹泻和伪膜性肠炎。然而，目前尚无预防艰难梭菌感染 (CDI) 的许可疫苗。在这项研究中，使用现代计算机方法设计了一种多表位疫苗。选择了两个靶蛋白，CdeC 影响孢子萌发，以及 fliD 影响繁殖体定植，来构建疫苗，以便同时诱导针对两种不同形式（孢子和繁殖体）的免疫反应。我们从国家生物技术信息中心 (NCBI) 数据库中获取了蛋白序列。经过层层筛选，最终选择了 5 个细胞毒性 T 细胞淋巴细胞 (CTL) 表位、5 个辅助 T 淋巴细胞 (HTL) 表位和 7 个 B 细胞线性表位用于疫苗构建。然后，为了增强设计疫苗的免疫原性，添加了佐剂来构建疫苗。Prabi 和 RaptorX 服务器分别用于预测疫苗的二维和三维 (3D) 结构。此外，我们还对疫苗结构进行了细化和验证。进行了分子对接和分子动力学 (MD) 模拟，以检查疫苗-Toll 样受体 (TLR) 复合物、疫苗主要组织相容性复合体 (MHC) 复合物和疫苗-B 细胞受体 (BCR) 复合物的相互作用模型。此外，还进行了免疫刺激、人群覆盖率和分子克隆。上述发现表明，最终配方疫苗对抗病原体具有前景，但需要更多研究人员进行验证。
