Abstract
BackgroundVisceral 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.MethodsBy 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.ResultsSelected 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.ConclusionsThe 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.
Highlights
Visceral leishmaniasis (VL) caused by dimorphic Leishmania species is a parasitic disease with high socioeconomic burden in endemic areas worldwide
We explored into the physicochemical properties and receptor binding interaction of the multi-epitope vaccine, followed by molecular dynamics simulation of the vaccine-receptor complex and simulation of immune response
While the in silico studies by Khatoon et al [66] and Singh et al [67] largely utilized available genomic databases of L. donovani to select vaccine targets, Dikhit et al [11, 70] performed thorough investigations involving in silico, in vitro and in vivo analysis to screen and validate immunogenic epitopes obtained from proteins that are increasingly expressed at the infective parasite stage
Summary
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. Leishmania donovani and L. infantum cause visceral leishmaniasis (VL), a neglected tropical disease and second only to malaria in parasitic cause of death. Sustained elimination cannot be possible without proper and prevailing immunity development in the endemic population against Leishmania parasites in the post-elimination era due to the chance of reservoir mediated re-emergence of the disease [3]. A vaccination strategy can induce longterm protection with proper immunity in order to prevent development of disease in the most economical way, regardless of its mode of implementation
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