Mohammad-Matin Karbalaee-Alinazari, Ava Hashempour, Ali Honari Jahromi, Hadi Ghasemi, Mohammad Soroosh Hajizade, Mozhan Abdollahi, Amin Zahmatkesh
Hepatitis C virus (HCV) remains a major global health burden, and its core protein is central to both viral replication and immune evasion. Here, we used an immunoinformatics approach to design a multiepitope vaccine directed against the HCV core protein. Several prediction platforms were applied to identify immunogenic regions that were antigenic, non-toxic, and non-allergenic; the twenty epitopes that met all of these criteria were joined by linkers and fused to 50S ribosomal protein L7/L12 and Pam2Cys adjuvants. The resulting construct was modeled, refined, and docked with Toll-like receptors (TLR2, TLR3, TLR4, TLR7, and TLR9), after which normal mode analysis (NMA) and molecular dynamics (MD) simulations were performed to assess its stability. The refined fusion protein showed favorable predicted binding to all of the receptors tested, and both NMA and MD indicated that the vaccine-TLR2 complex was conformationally stable. Immune simulation further predicted the production of anti-HCV antibodies and the activation of cellular immunity. Taken together, these findings identify the construct as a promising HCV vaccine candidate that now warrants experimental validation.