Immunoinformatics-guided design of a multiepitope mRNA vaccine candidate against Lassa virus

Abstract

Introduction Lassa fever remains a persistent public health challenge in West Africa, characterized by high morbidity and mortality. Despite its endemicity, no licensed vaccines are currently available, underscoring the urgent need for innovative vaccine strategies. This study implements immunoinformatics-guided approaches that enable the rapid identification of immunogenic epitopes, facilitating the rational design of mRNA-based vaccines that are safe, effective, and tailored to target specific viral proteins. Methods Protein sequences of the Lassa virus (LASV) glycoprotein complex (GPC), L-protein, and polymerase protein were retrieved from the NCBI database. HTL, CTL, and B-cells epitope predictions were performed using NetMHCpan-4.1, IEDB, and BepiPred 2.0. server, respectively. Predicted epitopes were assessed for antigenicity, allergenicity, toxicity, interleukins, and IFN-γ. High-scoring epitopes were assembled into a multiepitope construct linked by the appropriate linker, adjuvants, and translational regions. Secondary and tertiary structure predictions of the mRNA construct were refined, validated, and docked with human TLR-4 and TLR-7. Results The mRNA construct shows broad population coverage, particularly in West Africa. The physicochemical properties from ExpasyProtParam server compute a molecular weight of 140.44kDa, with lengths of 1,283 amino acids, an aliphatic index of 83.52, an instability index of 38.70, and a GRAVY score of -0.101. The Ramachandran plot for the validation of the tertiary construct shows that >90% of the amino acids are in the most favored region. The docking complexes scores with TLR-4 and TLR-7 result in -299.56 and -299.77, respectively, showing strong immunogenic potential. In-silico cloning into an mRNA expression vector demonstrated compatibility for mRNA synthesis and efficient antigen expression. Conclusion This study underscores the potential of immunoinformatics-driven mRNA vaccine design as a promising avenue for Lassa fever prevention. The predicted multiepitope mRNA construct offers a rational starting point for further experimental validation and preclinical development.