In a bid to develop a novel immunoprophylactic measure against visceral leishmaniasis (VL), MHC class-II-restricted epitopes of LdODC were identified by reverse vaccinology approach. Five consensus HLA-DRB1*0101-restricted epitopes were screened. The analysis revealed that the set of epitopes was presented by at least 54 diverse MHC class-II alleles. Based on in silico screening, followed by molecular dynamics simulation, population coverage analysis, and HLA cross-presentation ability, five best epitopes were evaluated. PBMCs isolated from treated VL subjects, when stimulated with synthetic peptide alone or as a cocktail of peptides, triggered a secretory IFN-γ, but not the IL-10 level. Support in this notion came from intracellular cytokine level with a considerable up-regulated IFN-γ produced by CD4+ T cells. Also, the enhanced IFN-γ seemed to be augmented with the activation of macrophages with prominent IL-12 production. Therefore, it can be concluded that the screened MHC class-II-restricted epitope hotspots derived from Leishmania ODC can trigger CD4+ T cells, which can skew macrophage functions towards protection. However, a detailed analysis can explore its potentiality as a vaccine candidate.

中文翻译：

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评估 LdODC 衍生的 MHC II 类限制肽对 VL 的免疫调节反应。

为了开发针对内脏利什曼病 (VL) 的新型免疫预防措施，通过反向疫苗学方法鉴定了 LdODC 的 MHC II 类限制性表位。筛选了五个共有的 HLA-DRB1*0101 限制性表位。分析表明，这组表位由至少 54 个不同的 MHC II 类等位基因呈现。基于计算机筛选，随后通过分子动力学模拟、群体覆盖分析和 HLA 交叉呈递能力，评估了五个最佳表位。从经治疗的 VL 受试者中分离出的 PBMC，在单独使用合成肽或作为肽混合物进行刺激时，会触发分泌型 IFN-γ，但不会触发 IL-10 水平。支持这一观点的是细胞内细胞因子水平，CD4+ T 细胞产生的 IFN-γ 显着上调。还，增强的 IFN-γ 似乎随着具有显着 IL-12 产生的巨噬细胞的激活而增强。因此，可以得出结论，筛选出的来自利什曼原虫 ODC 的 MHC II 类限制性表位热点可以触发 CD4+ T 细胞，从而使巨噬细胞功能偏向保护。然而，详细的分析可以探索其作为候选疫苗的潜力。