Leishmania spp. Proteome Data Sets: A Comprehensive Resource for Vaccine Development to Target Visceral Leishmaniasis

Abstract

Visceral leishmaniasis is a neglected infectious disease caused primarily by Leishmania donovani and Leishmania infantum protozoan parasites. A significant number of infections take a fatal course. Drug therapy is available but still costly and parasites resistant to first line drugs are observed. Despite many years of trial no commercial vaccine is available to date. However, development of a cost effective, needle-independent vaccine remains a high priority. Reverse vaccinology has attracted much attention since the term has been coined and the approach tested by Rappuoli and colleagues. This in silico selection of antigens from genomic and proteomic data sets was also adapted to aim at developing an anti-Leishmania vaccine. Here, an analysis of the efforts is attempted and the challenges to be overcome by these endeavors are discussed. Strategies that led to successful identification of antigens will be illustrated. Furthermore, these efforts are viewed in the context of anticipated modes of action of effective anti-Leishmania immune responses to highlight possible advantages and shortcomings.

In-depth quantitative proteomics uncovers specie-specific metabolic programs in Leishmania (Viannia) species

“…Assuming diploidy, L. braziliensis, L. panamensis and L. guyanensis strains used in this study contain 3.86 ± 0.1 pg, 3.89 ± 0.08 pg and 3.55 ± 0.2 pg of total protein per cell, respectively ( Fig 1B, Table 1). These values are similar to the protein estimation reported by Aebischer [39] for L. mexicana, which corresponds to~4 pg. Although we are aware that these calculations could vary according to the ploidy of the genome, the ploidy status of the strains here studied is unknown.…”

Differential Metabolic Pathway Analysis of the Proteomes of Leishmania donovani and Leptomonas seymouri

“…Also, defective metabolism, biosynthesis and replication of nucleic acids, flagellar movement and signaling of the parasite were observed as indicated by altered expression of proteins involved in these pathways. In silico selection of antigens from genomic and proteomic data sets has also been adapted with an aim to developing an anti‐ Leishmania vaccine. A proteome‐wide phylogenomic analysis to gain insights into Leishmania evolution, enabled the detection of genes that are shared in pathogenic Leishmania species, such as calpain‐like cysteine peptidases and 3'a2rel‐related proteins, or genes that could be associated with visceral or cutaneous development.…”

Immunogenicity of Potential CD4+ and CD8+ T Cell Epitopes Derived From the Proteome of Leishmania braziliensis

“…Although the Th1 immune profile has an important influence on the control of Leishmania infection, it has also been implicated in its pathogenesis. It has been described in murine models and also in humans, that high levels of TNF are associated with more severe forms of CL and chronicity, and the use of TNF inhibitors along with antiparasitic drugs have shown more promising disease outcomes (32)(33)(34)(35). Contradictory to what was expected, cells from SC subjects failed to mount a Th1 immune response upon peptide stimulation despite their higher proliferative capacity.…”