Multi-epitope vaccine eliciting robust immune responses against diverse Crimean-Congo hemorrhagic fever virus strains targeting the glycoprotein and RNA polymerase: An immunoinformatics-driven approach

Crimean-Congo hemorrhagic fever is a severe, life-threatening, tick-borne disease with reported case-fatality rate of up to 40%. Recognized by the World Health Organization as a priority because of its epidemic potential in more than 30 countries, it lacks effective treatment, making the urgent development of a vaccine crucial. In this study, we employed a state-of-the-art immunoinformatics-driven approach to design a multi-epitope subunit vaccine targeting diverse Crimean-Congo hemorrhagic fever virus strains. The proposed vaccine construct was predicted to be highly antigenic, nonallergenic, and nontoxic, with the potential to elicit strong humoral and cellular immune responses in the host. The final vaccine construct incorporated six cytotoxic T-lymphocyte epitopes, three helper T-lymphocyte epitopes, and two B-cell epitopes, which were predicted to be antigenic, nonallergenic, and nontoxic, with an estimated global population coverage of 99.31%. Structural quality assessment showed 93.1% of the residues in the most favored Ramachandran regions, an ERRAT score of 98.81, and a global mean pLDDT score of 74.63. Molecular docking and 300 ns molecular dynamics simulations predicted favorable interaction potential between the vaccine construct and TLR3 and TLR4, with stable behavior of the modeled receptor–vaccine complexes. Immune simulations predicted the potential for humoral and cellular immune responses, whereas codon optimization indicated favorable expression in Escherichia coli K-12. Collectively, these findings support the potential of the proposed broad-spectrum vaccine candidate and warrant further experimental validation.