An immunoinformatic approach driven by experimental proteomics: in silico design of a subunit candidate vaccine targeting secretory proteins of Leishmania donovani amastigotes

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

An Immunoinformatics Approach for SARS-CoV-2 in Latam Populations and Multi-Epitope Vaccine Candidate Directed towards the World’s Population

“…Comparative simulations using the C-IMMSIM algorithm have been conducted with experimentally validated peptides. Correlations with in vitro studies were found [165], which suggests that in vitro experiments with our construct may potentially evoke similar cellular behaviours.…”

“…The position and situation that our multi-epitope construct occupies has been found in other vaccine models constructed using different methods. Therefore, it seems to be relevant to the stabilization of the multi-epitope construct [165]. In addition to the immunogenicity and stability identified in our molecular dynamics analysis, the physicochemical analysis of the construct revealed other desirable characteristics related to a safer profile.…”

A Multi-Epitope Vaccine Against Sars-Cov-2 Directed Towards the Latin American Population: An Immunoinformatics Approach

“…There was a robust response to the third injection, with evidence of the production of IFN-1 and IL-2 cytokines related to CD8+ lineage expansion. Comparative simulations using C-IMMSIM algorithm have been conducted with experimentally validated peptides and correlations with in vitro studies were found 80 ; this suggests that in vitro experiments with our construct may potentially evoke similar cellular behaviours.…”

Intranasal vaccine from whole Leishmania donovani antigens provides protection and induces specific immune response against visceral leishmaniasis

“…Immuno-proteomic techniques are now extensively used to define immunogenic candidates in both promastigote and amastigote antigens [ 51 – 53 ]. Based on several previous studies highlighting the presence of highly immunogenic antigens in the promastigote form that initiates infection [ 54 – 56 ], we designed our prophylactic vaccine with total antigens from promastigote and identified the optimal mode of administration.…”