Next-gen vaccine design: Integrating proteomics and bioinformatics for japanese encephalitis

Japanese encephalitis is the most neglected tropical disease induced by a neuroinvasive flavivirus, which refers to the Japanese encephalitis virus (JEV). To date, no successful treatment strategies are available for this disease. Thus, utilizing immunoinformatics and reverse vaccinology, we designed a novel mRNA vaccine (JE-mVax) targeting the viral capsid protein, a precursor to the membrane M protein, and envelope protein using T and B lymphocyte epitopes. The epitopes were incorporated into JE-mVax after being validated as antigenic, non-allergenic, and non-toxic. Moreover, the epitopes achieved global coverage of 100% (combined MHC-I and MHC-II epitopes). Notably, the tertiary structure of JE-mVax achieved a TM-score of 0.49±0.15 and a C score of -1.90. After refinement, the structure demonstrated 93.617% amino acid residues in the most favorable region, an ERRAT score of 73.9899, and a Z score of -5.58. Subsequently, docking analysis showed that the JE-mVax had the lowest energy scores of -986.0 and -1314.2 KJ/mol for TLR-2 and TLR-4. However, the MMGBSA and molecular dynamic simulation analysis also validated this statement. Additionally, the JE-mVax exhibited efficient cloning in E. coli strains, and the immune simulation predicted that it might significantly induce T and B cells. Finally, MFE values of -355.20 kcal/mol (optimal) and -211.56 kcal/mol (centroid) predicted mRNA's marginal structural integrity and stability during host entrance, transcription, and expression. Nonetheless, comprehensive in vitro and in vivo validation is required to definitively demonstrate the vaccine candidate's safety and effectiveness profile.