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

• Published in: Vaccines (Basel) Vol. 9; no. 6; p. 658
• Main Authors: Rehman, Abdur, Ahmad, Sajjad, Shahid, Farah, Albutti, Aqel, Alwashmi, Ameen S. S., Aljasir, Mohammad Abdullah, Alhumeed, Naif, Qasim, Muhammad, Ashfaq, Usman Ali, Tahir ul Qamar, Muhammad
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 16.06.2021; MDPI
• Subjects: Accuracy; Adaptive immunity; Allergens; Amino acids; Antigens; Binding; Bioinformatics; Calcium; Cytotoxicity; E coli; Epitopes; Genomes; Immune system; Infections; Lymphocytes; Lymphocytes T; Major histocompatibility complex; MD simulation; Molecular docking; Molecular dynamics; Molecular interactions; Morbidity; multi-epitope vaccine; Parasites; Parasitic diseases; Peptides; Population; Proteins; Proteomics; Schistosoma haematobium; Schistosoma japonicum; Schistosoma mansoni; Schistosomiasis; Servers; TLR2 protein; TLR4 protein; Toll-like receptors; Vaccines; Virulence; Sub-Saharan Africa
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines9060658

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.