In-silico design of an immunoinformatics based multi-epitope vaccine against Leishmania donovani

Abstract

Background Visceral Leishmaniasis (VL) is a fatal vector-borne parasitic disorder occurring mainly in tropical and subtropical regions. VL falls under the category of neglected tropical diseases with growing drug resistance and lacking a licensed vaccine. Conventional vaccine synthesis techniques are often very laborious and challenging. With the advancement of bioinformatics and its application in immunology, it is now more convenient to design multi-epitope vaccines comprising predicted immuno-dominant epitopes of multiple antigenic proteins. We have chosen four antigenic proteins of Leishmania donovani and identified their T-cell and B-cell epitopes, utilizing those for in-silico chimeric vaccine designing. The various physicochemical characteristics of the vaccine have been explored and the tertiary structure of the chimeric construct is predicted to perform docking studies and molecular dynamics simulations. Results The vaccine construct is generated by joining the epitopes with specific linkers. The predicted tertiary structure of the vaccine has been found to be valid and docking studies reveal the construct shows a high affinity towards the TLR-4 receptor. Population coverage analysis shows the vaccine can be effective on the majority of the world population. In-silico immune simulation studies confirms the vaccine to raise a pro-inflammatory response with the proliferation of activated T and B cells. In-silico codon optimization and cloning of the vaccine nucleic acid sequence have also been achieved in the pET28a vector. Conclusion The above bioinformatics data support that the construct may act as a potential vaccine. Further wet lab synthesis of the vaccine and in vivo works has to be undertaken in animal model to confirm vaccine potency.

Immunoinformatics design of multivalent epitope vaccine against monkeypox virus and its variants using membrane-bound, enveloped, and extracellular proteins as targets

“…Using various in silico and immunoinformatics approaches, researchers have designed such vaccines against several pathogens-Zika virus, Respiratory syncytial virus, Dengue virus, Leishmania donovani, Mycobacterium Tuberculosis, etc. (70)(71)(72)(73)(74). Yu et al (75) developed an in silico multivalent vaccine model for SARS-CoV-2 and proved its immunogenicity through in vitro and in vivo experiments.…”

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.…”

Rapid and simultaneous multiepitope antigen-based detection of Enterococcus by microscale thermophoresis and immunomagnetic separation

“…A single antigenic molecule may have one or more distinct epitopes, and each epitope is specific for only one antigen. At present, the construction of multi-antigen epitopes is mainly used in vaccine design to combat diseases, including tumors and various pathogenic bacteria ( Al-Megrin et al, 2022 ; Saha et al, 2022 ). Mahdevar et al (2022) designed a novel multi-epitope vaccine against breast cancer, which comprised of the most immunodominant epitope of the BORIS cancer-testis antigen by using immune-informatics approach.…”