Brito Rory C F, Guimarães Frederico G, Velloso João P L, Corrêa-Oliveira Rodrigo, Ruiz Jeronimo C, Reis Alexandre B, Resende Daniela M
Laboratório de Pesquisas Clínicas, Programa de Pós-graduação em Ciências Farmacêuticas/CiPharma, Escola de Farmácia, Campus Morro do Cruzeiro, Universidade Federal de Ouro Preto, Bauxita, 35.400-000 Ouro Preto, Minas Gerais, Brazil.
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas, Campus Morro do Cruzeiro, Universidade Federal de Ouro Preto, Bauxita, 35.400-000 Ouro Preto, Minas Gerais, Brazil.
Int J Mol Sci. 2017 Feb 10;18(2):371. doi: 10.3390/ijms18020371.
Leishmaniasis is a wide-spectrum disease caused by parasites from genus. There is no human vaccine available and it is considered by many studies as apotential effective tool for disease control. To discover novel antigens, computational programs have been used in reverse vaccinology strategies. In this work, we developed a validation antigen approach that integrates prediction of B and T cell epitopes, analysis of Protein-Protein Interaction (PPI) networks and metabolic pathways. We selected twenty candidate proteins from tested in murine model, with experimental outcome published in the literature. The predictions for CD4⁺ and CD8⁺ T cell epitopes were correlated with protection in experimental outcomes. We also mapped immunogenic proteins on PPI networks in order to find Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with them. Our results suggest that non-protective antigens have lowest frequency of predicted T CD4⁺ and T CD8⁺ epitopes, compared with protective ones. T CD4⁺ and T CD8⁺ cells are more related to leishmaniasis protection in experimental outcomes than B cell predicted epitopes. Considering KEGG analysis, the proteins considered protective are connected to nodes with few pathways, including those associated with ribosome biosynthesis and purine metabolism.
利什曼病是一种由利什曼原虫属寄生虫引起的广谱疾病。目前尚无人类疫苗，许多研究认为它是疾病控制的一种潜在有效工具。为了发现新型抗原，计算程序已被用于反向疫苗学策略。在这项工作中，我们开发了一种验证抗原方法，该方法整合了B细胞和T细胞表位预测、蛋白质-蛋白质相互作用（PPI）网络分析和代谢途径分析。我们从文献中发表的小鼠模型实验结果中筛选了20种候选蛋白进行测试。CD4⁺和CD8⁺ T细胞表位的预测结果与实验结果中的保护作用相关。我们还在PPI网络上绘制了免疫原性蛋白，以找到与其相关的京都基因与基因组百科全书（KEGG）途径。我们的结果表明，与保护性抗原相比，非保护性抗原预测的T CD4⁺和T CD8⁺表位频率最低。在实验结果中，T CD4⁺和T CD8⁺细胞比B细胞预测表位与利什曼病保护的关系更密切。考虑到KEGG分析，被认为具有保护作用的蛋白质与较少途径的节点相连，包括那些与核糖体生物合成和嘌呤代谢相关的途径。
