Integrated Core Proteomics, Subtractive Proteomics, and Immunoinformatics Investigation to Unveil a Potential Multi-Epitope Vaccine against Schistosomiasis

Abstract

Schistosomiasis is a parasitic infection that causes considerable morbidity and mortality in the world. Infections of parasitic blood flukes, known as schistosomes, cause the disease. No vaccine is available yet and thus there is a need to design an effective vaccine against schistosomiasis. Schistosoma japonicum, Schistosoma mansoni, and Schistosoma haematobium are the main pathogenic species that infect humans. In this research, core proteomics was combined with a subtractive proteomics pipeline to identify suitable antigenic proteins for the construction of a multi-epitope vaccine (MEV) against human-infecting Schistosoma species. The pipeline revealed two antigenic proteins—calcium binding and mycosubtilin synthase subunit C—as promising vaccine targets. T and B cell epitopes from the targeted proteins were predicted using multiple bioinformatics and immunoinformatics databases. Seven cytotoxic T cell lymphocytes (CTL), three helper T cell lymphocytes (HTL), and four linear B cell lymphocytes (LBL) epitopes were fused with a suitable adjuvant and linkers to design a 217 amino-acid-long MEV. The vaccine was coupled with a TLR-4 agonist (RS-09; Sequence: APPHALS) adjuvant to enhance the immune responses. The designed MEV was stable, highly antigenic, and non-allergenic to human use. Molecular docking, molecular dynamics (MD) simulations, and molecular mechanics/generalized Born surface area (MMGBSA) analysis were performed to study the binding affinity and molecular interactions of the MEV with human immune receptors (TLR2 and TLR4) and MHC molecules (MHC I and MHC II). The MEV expression capability was tested in an Escherichia coli (strain-K12) plasmid vector pET-28a(+). Findings of these computer assays proved the MEV as highly promising in establishing protective immunity against the pathogens; nevertheless, additional validation by in vivo and in vitro experiments is required to discuss its real immune-protective efficacy.

A Comprehensive Computer Aided Vaccine Design Approach to Propose a Multi-Epitopes Subunit Vaccine against Genus Klebsiella Using Pan-Genomics, Reverse Vaccinology, and Biophysical Techniques

“…The subcellular localization of selected proteins was predicted through PSORTb 3.0 subcellular localization prediction tool [30]. The surface proteins were then filtered using several parameters to prioritize potential vaccine candidates for the pathogen [31][32][33][34].…”

In silico designing of vaccine candidate against Clostridium difficile

“…An adjuvant, Cholera Toxin B (CTB) was attached to the N-terminal of the vaccine using the EAAAK linker (Fig. 3 A), as it has been used for the construction of many fusion proteins and acts as a rigid spacer between the protein domains 49 – 51 . The addition of CTB adjuvants in vaccines improves the formation of a protective immunity as well as prevents chances of autoimmune reactions 52 .…”

Designing a Multi-Epitope Vaccine against Chlamydia trachomatis by Employing Integrated Core Proteomics, Immuno-Informatics and In Silico Approaches

“…Two properties were calculated and displayed using Xmgrace (Version 5.1.19. Available online: https://plasma-gate.weizmann.ac.il/Grace/ (accessed on 22 May 2021)) [68]. The root mean square deviation (RMSD) and radius of gyration (RoG) were used.…”

“…The MEBV sequence was uploaded to the JCat server (http://jcat.de/; accessed on 13 July 2021) for codon adaptation [74]. In silico cloning was performed to assure the expression of a multiepitope vaccine in an extensively employed E. coli pET28a (+) vector with the SnapGene v4.3 server [68].…”