Reverse vaccinology approach for identification of epitopes from E1 protein as peptide vaccine against HCV: A proof of concept

• Published in: Vaccine Vol. 42; no. 24; p. 126106
• Main Authors: Meshram, Rohan, Kolte, Baban, Gacche, Rajesh
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 24.10.2024; Elsevier Limited
• Subjects: Algorithms; Allergy and Immunology; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell activation; Chemical synthesis; Clinical trials; Computational Biology - methods; Computer applications; Cytokines; Cytokines - immunology; Cytokines - metabolism; Drug resistance; E1 protein; Energy; Epitopes; Epitopes - immunology; Epitopes, T-Lymphocyte - immunology; Free energy; Gibbs free energy; Global health; Glycoproteins; Granulocyte-macrophage colony-stimulating factor; HCV vaccine; Hepacivirus - immunology; Hepatitis C; Hepatitis C - immunology; Hepatitis C - prevention & control; Hepatitis C virus; Humans; Immunogenicity; immunoinformatics; Immunology; Informatics; interleukin-6; Lymphocytes; Lymphocytes T; Major histocompatibility complex; mechanism of action; Methods; MMPBSA free energy estimation; Molecular dynamics; Molecular Dynamics Simulation; Molecular dynamics simulations; Peptides; prediction; Proof of Concept Study; Protein Subunit Vaccines; Proteins; Public health; Simulation; Structural analysis; Structural integrity; T-cell activation; Tumor necrosis factor-α; vaccine development; Vaccines; Vaccines, Subunit - immunology; Vaccinology - methods; Viral Envelope Proteins - immunology; Viral Hepatitis Vaccines - immunology; India; Molecular dynamics simulations; HCV vaccine; MMPBSA free energy estimation; T-cell activation
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2024.07.007

[Display omitted] •Computational Identification of Epitopes on E1 glycoprotein in HCV.•Molecular Dynamics Simulations.•Advanced Free energy Estimations using MMPBSA.•Synthesis and characterization of candidate epitope peptides.•Assay for activation of CD4 + and CD8 + T cells using synthesized epitope peptides in healthy individuals, and HCV recovered Human subjects. The development of effective vaccines against Hepatitis C Virus (HCV) remains a global health priority and challenge. In this study, we employed an integrative approach combining computational epitope prediction with experimental validation to identify immunogenic peptides targeting the E1 glycoprotein of HCV. In the present report, computational data from various epitope prediction algorithms such as IEDB and SYFPEITHI, followed by molecular dynamics (MD) simulations and immuno-informatics analysis is presented. Through computational screening, we identified potential epitope candidates, with QVRNSSGLY (P3) and QLFTFSPRH (P7) emerging as promising candidates. MD simulations revealed stable interactions between these epitopes and MHC molecule, further validated by free energy estimations using MMPBSA method. Immuno-informatics analysis supported these findings, showing high binding potential and immunogenicity scores for the selected peptides. Subsequent synthesis and characterization of epitope peptides confirmed their structural integrity and purity required for conducting immune activation assays. Experimental immunological assays carried out in this study involved epitope peptide induced activation of CD8 + and CD4 + T cells from healthy human subjects and HCV- recovered patients. Data from experimental validation revealed significant cytokine release upon exposure to epitope peptides, particularly TNF-a, IL-6, and GM-CSF, indicative of robust immune responses. Notably, peptides P3 and P7 exhibited the most pronounced cytokine induction profiles, underscoring their potential as vaccine candidates. Further investigations addressing the mechanism of action of these epitope peptides under preclinical and clinical settings may help in developing effective vaccine against HCV.