Vaccine Development T-cell (MHC-I) Epitopes Identification Against the Indian HCV Genotype: An Approach Based on Immunoinformatic

Hepatitis C virus (HCV) infects approximately 58 million individuals worldwide, often progressing to chronic liver disease, cirrhosis, and hepatocellular carcinoma. The viral envelope glycoproteins E1 and E2 are critical for HCV entry and serve as primary targets for neutralizing antibodies. Recent advancements in cryo-electron tomography have provided high-resolution structures (3.5 & Aring;) of the E1E2 heterodimer, revealing interactions between the E1 and E2 ectodomains, as well as neutralizing antibody complexes (e.g., AR4A, AT1209, IGH505). This structural information facilitates the design of a synthetic peptide vaccine targeting conserved E1 and E2 regions. We suggest developing a vaccine tailored to the HLA-A*24:02 allele, the most prevalent in the Indian population. Epitope candidates will be screened using immunoinformatics tools, incorporating epitopes derived from epitope mapping with 7t6x protein structure modeling. Molecular docking studies will identify high-affinity interactions with human MHC-Class I alleles, using tools such as AutoDock and HADDOCK. GROMACS molecular dynamics simulations will assess peptide-HLA binding stability and dynamics. Among ten screened epitopes, KWEYVVLLF and QWQVLPCSF emerged as the most promising based on their toxicity profiles, conservation, and docking scores with HLA-A*24:02 (- 9.3 kcal/mol for KWEYVVLLF and - 225.34 kcal/mol for QWQVLPCSF). Molecular dynamics simulations indicated that the KWEY segment of KWEYVVLLF underwent structural changes, while the VVLLF region maintained stable binding to Chain A, suggesting immunogenic potential. These epitopes represent strong candidates for T-cell-based vaccines, and the reverse vaccinology approach, supported by computational tools, offers a population-specific strategy for HCV vaccine development, advancing precision immunotherapy.