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Broad Spectrum Peptide Vaccine Design Against Hepatitis C Virus
Sherly Kurnia Dewi1, Soegianto Ali1,2, Vivitri Dewi Prasasty1
1Faculty of Biotechnology, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia.
Insights
This study identified four promising peptides from Hepatitis C virus (HCV) proteins to develop a novel combinational peptide vaccine. These peptides aim to enhance immune responses against HCV infection.
Area of Science:
- Immunology and Virology
- Vaccine Development
Background:
- Hepatitis C virus (HCV) infection poses a significant global health challenge.
- Current limitations in vaccine development stem from weak cellular and humoral immune responses to HCV.
Purpose of the Study:
- To identify conserved epitopes from prevalent Indonesian HCV subtypes for vaccine design.
- To computationally predict potential B cell, CD8+ T cell, and CD4+ T cell epitopes.
Main Methods:
- Bioinformatic analysis of conserved regions in five Indonesian HCV subtypes.
- Epitope prediction using NetMHCPan, IEDB, LBtope, and Ig-Pred tools.
- In silico assessment of antigenicity, toxicity, stability, population coverage, and molecular interactions.
Main Results:
- Identified two potent B cell and CD8+ T cell epitopes (E1, E2) from the envelop protein.
- Selected two peptides from the NS3 protein as effective CD4+ T cell inducers.
- Evaluated epitopes for antigenicity, stability, and potential immunogenicity.
Conclusions:
- Four selected peptides show promise for a combinational peptide vaccine against HCV.
- Further in vivo studies are recommended to validate the vaccine's efficacy in inducing secondary immune responses.
Background:
Hepatitis C virus (HCV) infection is a global burden. There is no peptide vaccine found as modality to cure the disease is available due to the weak cellular immune response and the limitation to induce humoral immune response.
Methods:
Five predominated HCV subtypes in Indonesia (1a, 1b, 1c, 3a, and 3k) were aligned and the conserved regions were selected. Twenty alleles of class I MHC including HLA-A, HLA-B, and HLAC types were used to predict the potential epitopes by using NetMHCPan and IEDB. Eight alleles of HLA-DRB1, together with a combination of 3 alleles of HLA-DQA1 and 5 alleles of HLA-DQB1 were utilized for Class II MHC epitopes prediction using NetMHCIIPan and IEDB. LBtope and Ig- Pred were used to predict B cells epitopes. Moreover, proteasome analysis was performed by NetCTL and the stability of the epitopes in HLA was calculated using NetMHCStabPan for Class I. All predicted epitopes were analyzed for its antigenicity, toxicity, and stability. Population coverage, molecular docking and molecular dynamics were performed for several best epitopes.
Results:
The results showed that two best epitopes from envelop protein, GHRMAWDMMMNWSP (E1) and PALSTGLIHLHQN (E2) were selected as promising B cell and CD8+ T cell inducers. Other two peptides, LGIGTVLDQAETAG and VLVLNPSVAATLGF, taken from NS3 protein were selected as CD4+ T cell inducer.
Conclusion:
This study suggested the utilization of all four peptides to make a combinational peptide vaccine for in vivo study to prove its ability in inducing secondary response toward HCV.
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