Prokaryotically expressed IBDV VP2 virus-like particles: Stability and protective efficacy

Infectious bursal disease virus (IBDV) causes severe immunosuppression in chickens, and traditional vaccines have potential safety risks. Virus-like particles (VLPs) are ideal vaccine candidates with high immunogenicity and safety, but their stability mechanism remains unclear. The IBDV VP2 protein was expressed in Escherichia coli using the pColdII-SUMO-VP2 vector, and self-assembled into 20 nm VLPs after purification and tag removal. Stability assays showed VLPs were significantly more stable than monomeric VP2, remaining intact at 4°C for over 180 days. Circular dichroism (CD) and molecular dynamics (MD) simulations confirmed VLPs had higher α-helix content, lower solvent-accessible surface area (SASA) and more compact conformation; and RMSF analysis showed that in residues 180-200, monomeric VP2 flexibility increased slightly with temperature, while VLPs displayed significantly reduced flexibility at 37°C owing to inter-subunit conformational locking; this short-term anti-Arrhenius behavior could not predict long-term storage stability following Arrhenius kinetics. Animal experiments demonstrated the VLPs vaccine induced dose-dependent high antibody titers and provided complete protection against IBDV challenge without obvious bursal lesions. This study investigated the relationship between the stability and structure of VLPs, providing insights for the design of stable VLP vaccines, and provides a stable and effective IBDV VLPs vaccine candidate.