Abstract
The Lassa virus (LV) is a hemorrhagic virus that causes Lassa fever (LF). Despite its high mortality rate in Africa, no FDA-approved mRNA vaccine currently exists. Considering its epidemic potential, a new multi-epitope mRNA vaccine (LF-mVax) candidate is designed by immunoinformatics, targeting the GP, NP, and ZP through CD8+, CD4+, and B cell epitopes. LF-mVax was introduced with antigenic, non-allergic, and non-toxic epitopes that were derived from consensus sequences. The combined CD8 + and CD4 + epitopes provided 99.98% coverage of the global population, with robust immunity. Additionally, the selected epitopes were attached to adjuvants and linkers to make a stable, immunogenic vaccine against LV with favourable biophysical features. The analyses of the secondary and tertiary structures exhibit excellent quality (Ramachandran 82.4%, Z-score − 6.39), and the docking results show strong TLR-2 and TLR-4 binding (-1048.9 and − 1099.9 kJ/mol). The results were validated by MM-GBSA, MD simulation, PCA, and DCCM analysis. LF-mVax was cloned in E. coli (GC 45.83%, CAI 0.9962), and immune simulations predicted strong innate and adaptive responses with IL-2 and IFN-γ activation. The mRNA showed stability during entry, transcription, and expression in the host. Nevertheless, laboratory and animal studies are needed to establish the safety and potency of the LF-mVax. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-36965-6.