Abstract
Human and animal health is threatened by Hendra virus (HeV), which has few treatments. This in-silico vaccine design study focuses on HeV G (glycoprotein), F (fusion protein), and M (matrix protein). These proteins were computationally assessed for B and T-cell epitopes after considering HeV strain conservation, immunogenicity, and antigenicity. To improve vaccination immunogenicity, these epitopes were selectively ligated into a multiepitope construct. To improve vaccination longevity and immunological response, adjuvants and linkers were ligated. G, F, and M epitopes were used to create an mRNA HeV vaccine. Cytotoxic, helper, and linear B-lymphocytes' epitopes are targeted by this vaccine. The population coverage analysis demonstrates that multi-epitope vaccination covers 91.81 percent of CTL and 98.55 percent of HTL epitopes worldwide. GRAVY evaluated the vaccine's well-characterized physicochemical properties -0.503, indicating solubility and functional stability. Structure analysis showed well-stabilized 2° and 3° structures in the vaccine, with alpha helix, beta sheet, and coil structures (Ramachandran score of 88.5% and Z score of -3.44). There was a strong affinity as shown by docking tests with TLR-4 (central score of -1139.4 KJ/mol) and TLR-2 (center score of -1277.9 KJ/mol). The coupled V-apo, V-TLR2, and V-TLR4 complexes were tested for binding using molecular dynamics simulation where extremely stable complexes were found. The predicted mRNA structures provided significant stability. Codon optimization for Escherichia. coli synthesis allowed the vaccine to attain a GC content of 46.83% and a CAI score of 1.0, which supports its significant expression. Immunological simulations indicated vaccine-induced innate and adaptive immune reactions. Finally, this potential HeV vaccine needs more studies to prove its efficacy and safety.