Designing a novel mRNA vaccine against foot-and-mouth disease using immunoinformatics approach.

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-footed animals and has primarily been controlled through vaccination. The main disadvantages of the currently used whole virus-based inactivated vaccines are lack of immunological memory and requirement of strict bio-containment facility for upscaling the virus. In order to lower the burden of FMD, development of novel and potent vaccines is of paramount importance. Thus, this study resorted to immunoinformatics to design a multi-epitope- based mRNA vaccine that would protect against the FMD virus serotypes O, A, and Asia1. Several immunoinformatics tools were utilized to predict T and B-cell epitopes present on the capsid protein of FMD virus. These predicted epitopes were passed through a computational approach comprised of antigenicity, toxicity, allergenicity, and other biochemical properties-based prediction and analyses. Further, molecular docking and simulation among the predicted epitopes and MHC molecules was carried out to identify the key epitopes and MHC molecules. The structural analysis of antigenic epitopes and MHC alleles revealed their structures and binding sites. The seven predicted epitopes, a highly immunogenic adjuvant, secretion booster, and appropriate linkers, namely GPGPG and EAAAK, were combined to design the mRNA vaccine. The physicochemical analytical findings indicated that the vaccine construct found to be antigenic, almost neutral at physiological pH, non-toxic, non-allergenic, stable, and capable of generating a robust immune response. The findings of this comprehensive study demonstrated that this vaccine construct could pave the way for successfully combating infections caused by the economically important FMD virus. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-025-00444-z.