Immunoinformatics design of an mRNA vaccine against Langat virus

Langat virus, part of the tick-borne encephalitis virus complex in the Flavivirus family, is transmitted by ticks and, although not yet a human pathogen, poses a potential risk. To mitigate any future threat, an effective mRNA vaccine is essential, especially given the limitations of live attenuated vaccines for immunosuppressed individuals. This study focuses on developing an mRNA vaccine for Langat virus using immunoinformatics. Viral sequences from NCBI were analyzed for antigenicity, allergenicity, and toxicity, with predictions made for linear B cell, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) epitopes. The final vaccine constructs included 1 HTL, 2 LBL, and 2 CTL epitopes, evaluated for physicochemical properties, and secondary structure. Molecular docking with Toll-Like Receptors 7 and 8 (TLR 7 and TLR 8) revealed strong binding affinities. Population coverage analysis of selected major histocompatibility complex (MHC) alleles indicated the constructs' potential effectiveness globally. Immune simulation suggested moderate, early immune activation and potential for long-term immunity. Molecular dynamics simulations indicated a stable root mean square deviation (RMSD) trajectory. The constructs expressed effectively in E. coli using the pET28a vector, with the first construct showing the highest solubility (0.48), the second the lowest instability index (33.78), and the final construct the strongest immunogenicity. Collectively, these mRNA vaccine constructs show promising immunogenic potential against the Langat virus and other Flavivirus family members.