Department of Biotechnology, National Institute of Pharmaceutical Education & Research, Hajipur, India.
Division of Immunology, Rajendra Memorial Research Institute of Medical Sciences, Patna, India.
Parasite Immunol. 2020 Apr;42(4):e12699. doi: 10.1111/pim.12699. Epub 2020 Feb 6.
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.
为了开发针对内脏利什曼病 (VL) 的新型免疫预防措施，采用反向疫苗学方法鉴定了 MHC Ⅱ类限制的 LdODC 表位。筛选了 5 个共识 HLA-DRB1*0101 限制表位。分析表明，这组表位由至少 54 种不同的 MHC Ⅱ类等位基因呈递。基于计算机筛选、分子动力学模拟、群体覆盖分析和 HLA 交叉呈递能力，评估了 5 个最佳表位。用合成肽单独或作为肽混合物刺激来自经治疗的 VL 患者的 PBMC，引发了分泌型 IFN-γ，但不引发 IL-10 水平。这一观点得到了细胞内细胞因子水平的支持，CD4 T 细胞产生了相当高水平的上调 IFN-γ。此外，增强的 IFN-γ似乎随着巨噬细胞的激活和显著的 IL-12 产生而增加。因此，可以得出结论，从利什曼原虫 ODC 筛选出的 MHC Ⅱ类限制表位热点可以触发 CD4 T 细胞，从而使巨噬细胞的功能偏向于保护。然而，详细的分析可以探索其作为疫苗候选物的潜力。
