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In Vivo Infection with Leishmania amazonensis to Evaluate Parasite Virulence in Mice
Published on: February 20, 2020
Immunoinformatics Features Linked to Leishmania Vaccine Development: Data Integration of Experimental and In Silico
Rory C F Brito1,2, Frederico G Guimarães3, João P L Velloso4
1Laboratório 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. rorybrito@gmail.com.
Abstract:
Leishmaniasis is a wide-spectrum disease caused by parasites from Leishmania 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 Leishmania 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.
