Unleashing the Immune Arsenal: Development of Broad-spectrum Multiepitope Bluetongue Vaccine Targeting Conserved T Cell Epitopes of Structural Proteins 4777

Abstract Description Bluetongue (BT) is a severe arboviral disease of ruminants caused by Bluetongue virus (BTV), which has over 32 serotypes, complicating vaccine efficacy. The virus’s structural proteins are promising vaccine targets but exhibit significant amino acid polymorphism and inhibitory epitopes. This study focused on identifying highly conserved T cell epitopes within VP1, VP5, and VP7 proteins to design a broad-spectrum multiepitope vaccine for bovine and mouse models. Using immuno-informatics, we selected MHC-I and -II-restricted epitopes that are highly antigenic, non-allergenic, and non-toxic. CD4+ T cell epitopes also induced IFN-γ responses. The vaccine design incorporated TLR4-agonist adjuvants, beta-defensin 2, and the 50S ribosomal unit to enhance innate and cell-mediated immunity. Protein-protein docking revealed strong binding affinities, and 100-nanosecond molecular dynamics simulations confirmed stable interactions between the vaccine and TLR4. In silico vaccination studies demonstrated robust proinflammatory responses, supporting the vaccine’s potential to induce cross-reactive immunity. These results lay the foundation for further wet lab validation to assess immunogenicity, safety, and practical applicability in livestock. Funding Sources Tier 2 Canada Research Chair, CIHR 2021-00215 Topic Categories Veterinary and Comparative Immunology (VET)