A Multi-Domain Approach for Designing of Novel Epitopes-Based Vaccine Against Chandipura Virus

Abstract

Chandipura virus (CHPV), a member of the Rhabdoviridae family, poses a significant global health threat due to its association with acute encephalitis outbreaks, particularly among children. With its high fatality rate and recurrent incidences in endemic areas. The absence of an approved vaccine highlights the critical need for advanced approaches to address CHPV infections. In this study, integrated strategies, including reverse vaccinology, molecular docking, and molecular dynamics (MD) simulations, were used to identify novel epitopes for vaccine design against CHPV. In subtractive proteomic analysis, four proteins > YP_007641377.1 nucleocapsid protein, > YP_007641379.1 matrix protein, > YP_007641380.1 glycoprotein, and > YP_007641381.1 large protein, were chosen for epitope prediction, and both B cells and T cells were predicted. The predicted epitopes were further subjected to immunoinformatics screening, and eight epitopes were shortlisted for vaccine construction. The epitopes were linked by the GPGPG linker and additionally attached with Cholera Toxin B subunit (CTB) adjuvant by the EAAAK linker to improve the efficacy of the vaccine construct. The vaccine construct was further subjected to structure prediction and biophysics studies. In molecular docking analysis, the best docking interactions were indicated by the weighted scores and the lowest energy values. Notably, in the case of vaccine MHC-I, cluster 12 showed the most favorable binding with the lowest energy score of -838.0 kcal/mol. In the case of vaccine MHC-II, cluster 7 demonstrated the most stable interaction, with the lowest energy value of -948.7 kcal/mol, while in the case of vaccine TLR-4. Cluster 4 exhibited the most favorable binding, with both the weighted and lowest energy scores at -1175.3 kcal/mol, indicating a highly stable interaction. Moreover, the dynamic behavior of the docked molecules was further analyzed through (MD) simulations. The simulation analysis unveils that the vaccine construct and the target receptor binding affinity are stable during 50 simulation periods.