A computationally designed multi-epitope mRNA vaccine against Chandipura virus showed favorable TLR4 binding (ΔG = −16.6 kcal/mol) and structural stability in silico.
An in silico designed multi-epitope mRNA vaccine against Chandipura virus demonstrates favorable structural stability and predicted immune activation, providing a candidate for future experimental validation.
Chandipura virus (CHPV), a recently discovered member of the Rhabdoviridae family, has been linked to outbreaks of acute encephalitis in India, primarily affecting children and causing high mortality. Despite its clinical importance, no vaccine or targeted antiviral treatment is currently approved. This study used an integrated approach combining structure-guided reverse vaccinology and immunoinformatics to develop a multi-epitope vaccine candidate targeting the virus's glycoprotein. Selected epitopes include one B-cell epitope, four cytotoxic T lymphocyte (CTL) epitopes, and two helper T lymphocyte (HTL) epitopes, chosen for conservation, antigenicity, non-toxicity, and non-allergenicity. Sequence prediction and structural modeling identified epitopes with promising immunological and structural features. The final vaccine candidate was further analyzed for physicochemical properties, solubility, antigenicity, and allergenicity using various computational tools. Structural modeling and refinement indicated an acceptable-quality model, with 92.7% of residues in the most favored regions of the Ramachandran plot and a ProSA z-score of −5.19. Molecular docking with TLR4 yielded a HADDOCK score of −22.6 ± 29.2 and a predicted binding free energy (ΔG) of −16.6 kcal/mol, suggesting a potentially favorable interaction within the constraints of the docking model. Molecular dynamics (MD) simulations indicated that the complex maintained structural stability under the simulated conditions, while MM-GBSA analysis estimated a binding free energy of −107.28 ± 26.65 kcal/mol, reflecting model-dependent interaction energy trends. Immune simulation predicted the possible activation of humoral and cellular immune responses within the limitations of the computational framework. In silico cloning into an E. coli expression system suggested that the construct may be compatible with heterologous expression. Overall, this study presents a computationally derived multi-epitope vaccine construct against CHPV. However, all findings are based on in silico predictions and require experimental validation to confirm immunogenicity, safety, and protective efficacy.
Rao et al. (Wed,) conducted a other in Chandipura virus (CHPV). Multi-epitope mRNA vaccine candidate was evaluated on Structural stability and TLR4 binding affinity (in silico). A computationally designed multi-epitope mRNA vaccine against Chandipura virus showed favorable TLR4 binding (ΔG = −16.6 kcal/mol) and structural stability in silico.