Fundación Instituto de Inmunología de Colombia (FIDIC), Carrera 50 No. 26-20, Post Code: 111321, Bogotá, Colombia; Universidad del Rosario, Carrera 24 No. 63C-69, Post Code: 111321, Bogotá, Colombia.
Fundación Instituto de Inmunología de Colombia (FIDIC), Carrera 50 No. 26-20, Post Code: 111321, Bogotá, Colombia; Universidad del Rosario, Carrera 24 No. 63C-69, Post Code: 111321, Bogotá, Colombia.
Bioorg Med Chem. 2018 May 15;26(9):2401-2409. doi: 10.1016/j.bmc.2018.03.044. Epub 2018 Apr 4.
Mycobacterium tuberculosis is considered one of the most successful pathogens in the history of mankind, having caused 1.7 million deaths in 2016. The amount of resistant and extensively resistant strains has increased; BCG has been the only vaccine to be produced in more than 100 years though it is still unable to prevent the disease's most disseminated form in adults; pulmonary tuberculosis. The search is thus still on-going for candidate antigens for an antituberculosis vaccine. This paper reports the use of a logical and rational methodology for finding such antigens, this time as peptides derived from the Rv3587c membrane protein. Bioinformatics tools were used for predicting mycobacterial surface location and Rv3587c protein structure whilst circular dichroism was used for determining its peptides' secondary structure. Receptor-ligand assays identified 4 high activity binding peptides (HABPs) binding specifically to A549 alveolar epithelial cells and U937 monocyte-derived macrophages, covering the region between amino acids 116 and 193. Their capability for inhibiting Mtb H37Rv invasion was evaluated. The recognition of antibodies from individuals suffering active and latent tuberculosis and from healthy individuals was observed in HABPs capable of avoiding mycobacterial entry to host cells. The results showed that 8 HABPs inhibited such invasion, two of them being common for both cell lines: 39265 (VLAAYVYSLDNKRLWSNLDT) and 39266 (APSNETLVKTFSPGEQVTTY). Peptide 39265 was the least recognised by antibodies from the individuals' sera evaluated in each group. According to the model proposed by FIDIC regarding synthetic vaccine development, peptide 39265 has become a candidate antigen for an antituberculosis vaccine.
结核分枝杆菌被认为是人类历史上最成功的病原体之一，在 2016 年导致了 170 万人死亡。耐药和广泛耐药菌株的数量有所增加；尽管卡介苗是 100 多年来唯一生产的疫苗，但它仍然无法预防成人中最广泛传播的肺结核形式。因此，人们仍在寻找抗结核疫苗的候选抗原。本文报告了使用一种逻辑和合理的方法来寻找这些抗原，这次是从 Rv3587c 膜蛋白衍生的肽。生物信息学工具用于预测分枝杆菌表面位置和 Rv3587c 蛋白结构，而圆二色性用于确定其肽的二级结构。受体-配体测定鉴定了 4 种高活性结合肽（HABP），它们特异性地结合到 A549 肺泡上皮细胞和 U937 单核细胞衍生的巨噬细胞上，覆盖了氨基酸 116 到 193 之间的区域。评估了它们抑制 Mtb H37Rv 入侵的能力。在能够避免分枝杆菌进入宿主细胞的 HABP 中，观察到来自活动性和潜伏性肺结核患者以及健康个体的抗体的识别。结果表明，有 8 种 HABP 抑制了这种入侵，其中两种对两种细胞系都是共同的：39265（VLAAYVYSLDNKRLWSNLDT）和 39266（APSNETLVKTFSPGEQVTTY）。肽 39265 是在每个组中评估的个体血清抗体识别最少的。根据 FIDIC 提出的关于合成疫苗开发的模型，肽 39265 已成为抗结核疫苗的候选抗原。
