Bovine viral diarrhea virus (BVDV) poses substantial economic burdens to global cattle industries. To address this, we designed an innovative multi-epitope vaccine targeting BVDV via immuno-informatics. Seven cytotoxic T lymphocyte (CTL), five helper T lymphocyte (HTL), and seven B-cell epitopes from E0/E2 glycoproteins were strategically connected using AAY, GPGPG, and KK linkers. To boost immunogenicity, a β-defensin adjuvant was incorporated at the N-terminal of the vaccine using a short peptide linker EAAAK.  Computational analysis confirmed favorable physiochemical properties, antigenicity, solubility, and safety (non-allergenic, non-toxic). Structural optimization yielded a stable vaccine's 3D model with improved Z-score (-2.67). Molecular docking revealed strong interactions between the vaccine and bovine TLR2 and TLR4. Molecular dynamics analysis confirmed the stability of the docked vaccine-TLR complexes. Immune simulation predicted robust humoral responses (elevated IgG/IgM) and cellular immunity (increased IFN-γ/IL-2). The codon-optimized sequence showed significant potential for high-level expression in E. coli. The newly designed chimeric E0/E2 epitope vaccine shows promise for triggering dual immune responses, offering a viable strategy for BVDV control.

To Cite This Article: Liang S, Wei M, Zhou W and Pang F, 2025. Immunoinformatics-driven engineering of a chimeric E0/E2 epitope vaccine targeting bovine viral diarrhea virus. Pak Vet J. http://dx.doi.org/10.29261/pakvetj/2025.201