Immuno-Informatics Analysis of Pakistan-Based HCV Subtype-3a for Chimeric Polypeptide Vaccine Design

Abstract

Hepatitis C virus (HCV) causes chronic and acute hepatitis infections. As there is extreme variability in the HCV genome, no approved HCV vaccine has been available so far. An effective polypeptide vaccine based on the functionally conserved epitopes will be greatly helpful in curing disease. For this purpose, an immuno-informatics study is performed based on the published HCV subtype-3a from Pakistan. First, the virus genome was translated to a polyprotein followed by a subsequent prediction of T-cell epitopes. Non-allergenic, IFN-γ producer, and antigenic epitopes were shortlisted, including 5 HTL epitopes and 4 CTL, which were linked to the final vaccine by GPGPG and AAY linkers, respectively. Beta defensin was included as an adjuvant through the EAAAK linker to improve the immunogenicity of the polypeptide. To ensure its safety and immunogenicity profile, antigenicity, allergenicity, and various physiochemical attributes of the polypeptide were evaluated. Molecular docking was conducted between TLR4 and vaccine to evaluate the binding affinity and molecular interactions. For stability assessment and binding of the vaccine-TLR4 docked complex, molecular dynamics (MD) simulation and MMGBSA binding free-energy analyses were conducted. Finally, the candidate vaccine was cloned in silico to ensure its effectiveness. The current vaccine requires future experimental confirmation to validate its effectiveness. The vaccine construct produced might be useful in providing immune protection against HCV-related infections.

Development of a Novel Multi-Epitope Vaccine Against Crimean-Congo Hemorrhagic Fever Virus: An Integrated Reverse Vaccinology, Vaccine Informatics and Biophysics Approach

“…The designed MEV was found to be highly antigenic, immunogenic, soluble, thermostable, and non-allergenic, demonstrating the epitope vaccine’s ability to elicit robust immune responses without causing allergic reactions. Tertiary and secondary structures provide information about a protein’s function, interactions with other proteins/ligands, and dynamics ( 77 ). The desirable characteristics of MEV improved significantly after predicted 3D structure refinement.…”

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

“…Virulent proteins are a primary target for vaccine candidates because they play a significant role in pathogenesis [35,36]. The nonredundant set of proteins were used in BLASTp search against the core virulent factor database (VFDB) [37] and those having sequence identity ≥30% and bit score >100 were selected.…”

Quest for Novel Preventive and Therapeutic Options Against Multidrug-Resistant Pseudomonas aeruginosa

“…The immune simulations generated a consistent increase in the number of antigens and antibodies which depicts a harmonious increment in immune responses. Further, the immunoreactivity of the vaccine model was evaluated by its expression in E. coli (K12) (Ahmad et al 2021 ), an appropriate host expression system. The optimization of the codon generated relevant CAI index (0.993) and GC content (55.7%) which are representatives of the suitable expression of the designed protein in the microorganism.…”