Computational Design of a Multiepitope Vaccine Targeting Rabies Virus Glycoprotein

Rabies, a neglected tropical disease, persists as a historical health challenge. The glycoprotein (G) gene of the rabies virus is the key antigen providing effective protection. Post-exposure prophylaxis involves vaccination and Rabies Immunoglobulins (RIGs) as per WHO guidelines. Identifying epitopes is crucial for specific immunotherapies. In this study, eight conserved epitopes were identified based on antigenicity, immunogenicity, MHC binding affinity, and IFN-[Formula: see text] stimulation. A multiepitope vaccine was constructed and validated for antigenicity, stability, and safety. Protein–protein docking revealed RGP6 and RGP7 as strong candidates, with RGP6 showing the highest docking scores (–7.351 and –5.197) and potential as a novel target epitope for immunotherapy. The molecular dynamics simulations demonstrated that both 6LGX-ligand and 6LGW-ligand complexes maintained structural stability and dynamic equilibrium over the course of the simulation. Further, the binding free energy calculations for 6LGX (–79.440) and 6LGW (–47.338) suggest that the 6LGX-ligand complex is more stable than the 6LGW-ligand complex, as evidenced by their more negative values, indicating greater energy required for dissociation. The study suggests that the multi-epitope subunit vaccine is immunogenic, nonallergic, and capable of eliciting cellular and humoral immune responses.