Infectious bursal disease virus (IBDV) remains a major global threat to poultry, causing severe immunosuppression and substantial economic losses. Existing vaccines live-attenuated, inactivated, and subunit provide incomplete protection and face challenges of safety, antigenic mismatch, and repeated dosing requirements. Nano-adjuvant technologies offer a transformative solution, enhancing vaccine immunogenicity, stability, and targeted delivery. Platforms include lipid nanoparticles, polymeric systems, virosomes, mesoporous silica, polysaccharides, and nanoemulsions elicit robust humoral and cellular immune responses, promote Th1/Th2 balance, and enable dose-sparing strategies. Toll-like receptor agonist-loaded nano-adjuvants further amplify dendritic cell activation, antigen presentation, and durable memory responses. Virus-like particles and virosomes structurally mimic IBDV antigens, enhancing immunogenicity without the risks of viral replication. Rational integration of precise antigen selection, multifunctional nano-adjuvants, and advanced delivery approaches promises next-generation vaccines capable of broad, long-lasting protection against very virulent and emerging IBDV variants. These innovations have the potential to revolutionize poultry vaccination, offering safer, more effective, and globally deployable strategies to safeguard poultry health and productivity.

Infectious bursal disease virus (IBDV) causes immunosuppression and bursal damage in chickens, and safer recombinant vaccines that provide durable protection are needed. This study compared the antigenicity, immunogenicity, protective efficacy, safety and antibody persistence of unpurified VP2 preparations and purified VP2 virus-like particles (VLPs) derived from the B87 and HLJ0504 IBDV strains. Recombinant VP2 proteins were expressed in Escherichia coli, purified and characterized, formulated with oil adjuvant and evaluated in specific-pathogen-free White Leghorn chickens. Both VP2 proteins retained antigenicity and assembled into relatively uniform VLPs of approximately 25 nm. Purified VLPs induced stronger antibody responses than corresponding unpurified preparations, with 10 µg producing the highest responses. In a virus neutralization assay, HLJ0504 VP2-based preparations induced the highest neutralizing-antibody titers. Following challenge with virulent IBDV BC6/85, 10 µg of HLJ0504 VLPs and unpurified HLJ0504 VP2 at an agar-gel precipitation titer of 1:10 each protected nine of 10 chickens, similar to a commercial inactivated vaccine, and preserved bursal architecture. No systemic or injection-site adverse reactions were detected and selected recombinant vaccines maintained elevated serum-antibody levels for 20 weeks. Thus, HLJ0504 VP2-based vaccines, particularly the VLPs formulation, are promising safe and protective candidates for controlling infectious bursal disease.