An immunoinformatic approach driven by experimental proteomics: in silico design of a subunit candidate vaccine targeting secretory proteins of Leishmania donovani amastigotes
Open Access
- 15 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Parasites & Vectors
- Vol. 13 (1), 1-21
- https://doi.org/10.1186/s13071-020-04064-8
Abstract
Visceral leishmaniasis (VL) caused by dimorphic Leishmania species is a parasitic disease with high socioeconomic burden in endemic areas worldwide. Sustaining control of VL in terms of proper and prevailing immunity development is a global necessity amid unavailability of a prophylactic vaccine. Screening of experimental proteome of the human disease propagating form of Leishmania donovani (amastigote) can be more pragmatic for in silico mining of novel vaccine candidates. By using an immunoinformatic approach, CD4+ and CD8+ T cell-specific epitopes from experimentally reported L. donovani proteins having secretory potential and increased abundance in amastigotes were screened. A chimera linked with a Toll-like receptor 4 (TLR4) peptide adjuvant was constructed and evaluated for physicochemical characteristics, binding interaction with TLR4 in simulated physiological condition and the trend of immune response following hypothetical immunization. Selected epitopes from physiologically important L. donovani proteins were found mostly conserved in L. infantum, covering theoretically more than 98% of the global population. The multi-epitope chimeric vaccine was predicted as stable, antigenic and non-allergenic. Structural analysis of vaccine-TLR4 receptor docked complex and its molecular dynamics simulation suggest sufficiently stable binding interface along with prospect of non-canonical receptor activation. Simulation dynamics of immune response following hypothetical immunization indicate active and memory B as well as CD4+ T cell generation potential, and likely chance of a more Th1 polarized response. The methodological approach and results from this study could facilitate more informed screening and selection of candidate antigenic proteins for entry into vaccine production pipeline in future to control human VL.Keywords
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This publication has 133 references indexed in Scilit:
- High-throughput prediction of protein antigenicity using protein microarray dataBioinformatics, 2010
- Phosphoproteome dynamics reveal heat-shock protein complexes specific to the Leishmania donovani infectious stageProceedings of the National Academy of Sciences of the United States of America, 2010
- Identification and Characterization of a Novel Deoxyhypusine Synthase in Leishmania donovaniOnline Journal of Public Health Informatics, 2010
- Improving physical realism, stereochemistry, and side‐chain accuracy in homology modeling: Four approaches that performed well in CASP8Proteins-Structure Function and Bioinformatics, 2009
- Predicting linear B‐cell epitopes using string kernelsJournal of Molecular Recognition, 2008
- Leishmania-released nucleoside diphosphate kinase prevents ATP-mediated cytolysis of macrophagesMolecular and Biochemical Parasitology, 2008
- Analysis of the Leishmania donovani transcriptome reveals an ordered progression of transient and permanent changes in gene expression during differentiationMolecular and Biochemical Parasitology, 2007
- NCBI reference sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteinsNucleic Acids Research, 2007
- AlgPred: prediction of allergenic proteins and mapping of IgE epitopesNucleic Acids Research, 2006
- Predicting transmembrane protein topology with a hidden markov model: application to complete genomesJournal of Molecular Biology, 2001