Abstract
<jats:p>Fowl adenovirus serotype 11 (FAdV-11) is an important viral pathogen affecting both broiler and layer chickens and is the primary causative agent of inclusion body hepatitis (IBH), resulting in substantial economic losses through reduced meat and egg production worldwide. Despite its economic significance, no commercial vaccine is currently available specifically against FAdV-11. In the present study, to the best of our knowledge, the first immunoinformatics-based multi-epitope vaccine candidate against FAdV-11 was designed using conserved regions of the penton and fiber proteins. Conserved B-cell, cytotoxic T-lymphocyte (CTL), and helper T-lymphocyte (HTL) epitopes were identified, screened for antigenicity, allergenicity, toxicity, and immunogenicity, and assembled into a multi-epitope vaccine construct using appropriate linker peptides and a β-defensin adjuvant. The designed vaccine exhibited favorable physicochemical properties and was predicted to be highly antigenic, non-allergenic, and non-toxic. Secondary and tertiary structure prediction, refinement, and validation confirmed the structural stability and reliability of the vaccine construct. Molecular docking and molecular dynamics simulation analysis demonstrated stable interactions with immune-related Toll-like receptors (TLRs), while immune simulation predicted robust humoral and cellular immune responses with the establishment of long-term immunological memory. Codon optimization yielded a Codon Adaptation Index (CAI) of 0.982, and in silico cloning into the pET-28a(+) expression vector suggested efficient recombinant expression in Escherichia coli. Collectively, these findings indicate that the proposed vaccine represents a promising candidate for the prevention of FAdV-11-induced IBH in poultry. Nevertheless, comprehensive in vitro and in vivo studies are required to validate its immunogenicity, safety, and protective efficacy.</jats:p>