Structure-guided computational design of a multi-epitope vaccine construct targeting Chandipura virus

Background Chandipura virus (CHPV) remains as a neglected pathogen with high mortality and no licensed vaccines available yet. In this study, the immuno-informatics approach was utilized for designing a multi-epitope vaccine, focusing on the conserved antigenic regions of CHPV. Methods Immunogenic protein sequences of the glycoprotein, matrix protein, nucleocapsid protein, and phosphoprotein were retrieved and screened for conserved regions using multiple sequence alignment, which revealed 49 conserved regions across the viral proteome. Results Epitope prediction identified 24 CTL, 8 HTL, and 7 B-cell epitopes with antigenicity and non-allergenicity properties. The selected epitopes were assembled into a single vaccine construct. The secondary and tertiary structure predictions were performed and further refined using GalaxyRefine to improve structural stability. PROCHECK analysis revealed that in the refined model, 93.5% of residues are present in the most favored Ramachandran regions. HADDOCK docking analysis demonstrated strong binding affinity to innate immune receptors, with PRODIGY binding energies as −11.8 kcal/mol, −14.5 kcal/mol, −18.8 kcal/mol, and −14.2 kcal/mol for TLR2/1, TLR3, TLR4, and TLR8, respectively. Codon optimization was performed, and the sequence was cloned into the pET-28a(+) plasmid. The immune simulation analysis predicted that the developed CHPV multi-epitope vaccine construct can induce antibody production and suggested the potential for long-term immune memory against CHPV. Conclusion In this study, we have designed a multi-epitope vaccine candidate against CHPV using conserved antigenic regions from multiple viral proteins, and in silico analyses indicated favorable antigenicity, structural stability, receptor interactions, and the potential to induce robust and long-lasting immune responses. The computational findings highlight the promise of the proposed vaccine against CHPV; however, experimental validation is essential to confirm its safety, immunogenicity, and protective efficacy.