Immunoinformatics Studies and Design of a Potential Multi-Epitope Peptide Vaccine to Combat the Fatal Visceral Leishmaniasis

Abstract

Leishmaniasis is a neglected tropical disease caused by parasitic intracellular protozoa of the genus Leishmania. The visceral form of this disease caused by Leishmania donovani continues to constitute a major public health crisis, especially in countries of endemicity. In some cases, it is asymptomatic and comes with acute and chronic clinical outcomes such as weight loss, pancytopenia, hepatosplenomegaly, and death if left untreated. Over the years, the treatment of VL has relied solely on chemotherapeutic agents, but unfortunately, these drugs are now faced with challenges. Despite all efforts, no successful vaccine has been approved for VL. This could be as a result of limited knowledge/understanding of the immune mechanisms necessary to regulate parasite growth. Using a computational approach, this study explored the prospect of harnessing the properties of a disulfide isomerase protein of L. donovani amastigotses to develop a multi-epitope subunit vaccine candidate against the parasite. We designed a 248-amino acid multi-epitope vaccine with a predicted antigenicity probability of 0.897372. Analyses of immunogenicity, allergenicity, and multiple physiochemical parameters indicated that the constructed vaccine candidate was stable, non-allergenic, and immunogenic, making it compatible with humans and hence, a potentially viable and safe vaccine candidate against Leishmania spp. Parasites.

Immunoinformatics Approach to Design a Multi-Epitope Nanovaccine against Leishmania Parasite: Elicitation of Cellular Immune Responses

“…The selected proteins were identified using an hierarchical proteome subtractive analysis using the whole proteome of the three different Leishmania species, an approach that has been previously applied on the proteome of L. braziliensis for the development of an anti- Leishmania vaccine [ 75 ]. On the contrary, the majority of research targeting the development of multi-epitope vaccines applies bioinformatic analysis using known antigenic Leishmania proteins with specific function [ 76 , 77 , 78 , 79 , 80 , 81 ]. Our analysis unveiled 232 conserved proteins among species which were further shortlisted to 66 based on their antigenicity evaluation using two different algorithms, VaxiJen and AntigenPro.…”

Development of a multi-epitope vaccine candidate for leishmanial parasites applying immunoinformatics and in vitro approaches

“…As the multi-epitope vaccines are designed to enhance the summative effect of cellular, humoral, and innate immune responses, they possess an edge over the monovalent candidates/formulations (41). Recently, several attempts have been made to employ the immunoinformatics approach for designing and assessing multi-epitope vaccine constructs for leishmanial parasites (42)(43)(44)(45)(46). In this study, a new multi-epitope vaccine candidate has been proposed from LdMAcP that plays a substantial role in parasitic virulence.…”

Immunoinformatics for Novel Multi-Epitope Vaccine Development in Canine Parvovirus Infections

“…The aliphatic index of the vaccine was calculated as 73.97, indicating that the vaccine is stable over a wide temperature range [ 94 ]. The theoretical pI of the proposed vaccine was set at 5.51, suggesting that the vaccine has acidic properties and is similar to those of MEV candidates against fatal visceral leishmaniasis [ 95 ]. The GRAVY score was calculated as −0.388; this negative value indicates that the vaccine interacts better with water molecules [ 96 , 97 ].…”