School of Life Sciences, Central University of Himachal Pradesh, District-Kangra, Shahpur, Himachal Pradesh, 176206, India.
Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow, 226025, India.
Arch Microbiol. 2022 Sep 7;204(10):604. doi: 10.1007/s00203-022-03219-8.
The protozoa Leishmania donovani causes visceral leishmaniasis (kala-azar), the third most common vector-borne disease. The visceral organs, particularly the spleen, liver, and bone marrow, are affected by the disease. The lack of effective treatment regimens makes curing and eradicating the disease difficult. The availability of complete L. donovani genome/proteome data allows for the development of specific and efficient vaccine candidates using the reverse vaccinology method, while utilizing the unique sequential and structural features of potential antigenic proteins to induce protective T cell and B cell responses. Such shortlisted candidates may then be tested quickly for their efficacy in the laboratory and later in clinical settings. These antigens will also be useful for designing antigen-based next-generation sero-diagnostic assays. L. donovani's cell surface-associated proteins and secretory proteins are among the first interacting entities to be exposed to the host immune machinery. As a result, potential antigenic epitope peptides derived from these proteins could serve as competent vaccine components. We used a stepwise filtering-based in silico approach to identify the entire surface-associated and secretory proteome of L. donovani, which may provide rationally selected most exposed antigenic proteins. Our study identified 12 glycosylphosphatidylinositol-anchored proteins, 45 transmembrane helix-containing proteins, and 73 secretory proteins as potent antigens unique to L. donovani. In addition, we used immunoinformatics to identify B and T cell epitopes in them. Out of the shortlisted surface-associated and secretory proteome, 66 protein targets were found to have the most potential overlapping B cell and T cell epitopes (linear and conformational; MHC class I and MHC class II).
利什曼原虫（Leishmania donovani）引起内脏利什曼病（黑热病），这是第三大常见的虫媒病。疾病会影响内脏器官，特别是脾脏、肝脏和骨髓。由于缺乏有效的治疗方案，因此治愈和根除该疾病非常困难。完整的利什曼原虫基因组/蛋白质组数据的可用性允许使用反向疫苗学方法开发特定和有效的疫苗候选物，同时利用潜在抗原蛋白的独特顺序和结构特征来诱导保护性 T 细胞和 B 细胞反应。这些被选中的候选物可以在实验室和临床环境中快速测试其功效。这些抗原也将有助于设计基于抗原的下一代血清诊断检测。利什曼原虫的细胞表面相关蛋白和分泌蛋白是最早与宿主免疫机制相互作用的实体之一。因此，从这些蛋白质中衍生的潜在抗原表位肽可以作为有能力的疫苗成分。我们使用基于逐步过滤的计算方法来鉴定利什曼原虫的整个表面相关和分泌蛋白质组，这可能提供经过合理选择的最暴露的抗原蛋白。我们的研究鉴定了 12 种糖基磷脂酰肌醇锚定蛋白、45 种含有跨膜螺旋的蛋白和 73 种分泌蛋白，它们是利什曼原虫特有的潜在抗原。此外，我们使用免疫信息学来鉴定它们中的 B 细胞和 T 细胞表位。在被选中的表面相关和分泌蛋白质组中，有 66 种蛋白质靶标被发现具有最潜在的重叠 B 细胞和 T 细胞表位（线性和构象；MHC 类 I 和 MHC 类 II）。
