AUTHOR=Yazdani Zahra , Rafiei Alireza , Yousefiyan Ali , Jaberi Keyvan TITLE=Design and computational analysis of a multi-epitope based peptide vaccine for the Crimean-Congo hemorrhagic fever virus JOURNAL=Acta Virologica VOLUME=Volume 69 - 2025 YEAR=2025 URL=https://www.frontierspartnerships.org/journals/acta-virologica/articles/10.3389/av.2025.14659 DOI=10.3389/av.2025.14659 ISSN=1336-2305 ABSTRACT=In this study, a combination of bioinformatics tools was employed to design a multi-epitope peptide-based vaccine against the Crimean-Congo hemorrhagic fever virus (CCHFV). The vaccine construct incorporates immunodominant epitopes derived from the envelopment polyprotein and the RNA-dependent RNA polymerase (L protein) of the Nigerian strain of CCHFV. Two potent adjuvants were included in the design to enhance immunogenicity. The structural and immunological characteristics of the vaccine were thoroughly evaluated. Both secondary and tertiary (3D) structure predictions were performed. The results indicated that the vaccine is antigenic and non-allergenic. Three-dimensional B-cell epitope prediction revealed that 108 residues within the construct are conformational (discontinuous) B-cell epitopes. Molecular docking and dynamic simulations with Toll-like receptors (TLRs) 2, 3, and 8 demonstrated stable interactions between the vaccine and these immune receptors. In silico cloning and mRNA stability analyses suggested that the construct is suitable for expression in Escherichia coli. Additionally, immune simulation results indicated that the vaccine could elicit a robust adaptive immune response following administration. Overall, the designed multi-epitope vaccine candidate demonstrates high structural quality and favorable immunological properties, supporting its potential to induce protective immunity against CCHFV.