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

Area of Science:

• Veterinary Virology
• Vaccine Development
• Structural Biology

Background:

• Infectious Bursal Disease Virus (IBDV) causes significant immunosuppression in chickens.
• Traditional IBDV vaccines pose potential safety concerns.
• Virus-like particles (VLPs) present a promising alternative due to high immunogenicity and safety, but their stability mechanisms require elucidation.

Purpose of the Study:

• To investigate the structural basis for the stability of IBDV virus-like particles (VLPs).
• To evaluate the efficacy of IBDV VLPs as a vaccine candidate.
• To provide insights for designing more stable VLP vaccines.

Main Methods:

• Expression of IBDV VP2 protein in Escherichia coli and self-assembly into VLPs.
• Stability assays at 4°C and 37°C.
• Circular dichroism (CD) and molecular dynamics (MD) simulations for structural analysis.
• Animal vaccination experiments to assess immunogenicity and protection.

Main Results:

• IBDV VLPs demonstrated enhanced stability compared to monomeric VP2, remaining intact for over 180 days at 4°C.
• Structural analyses revealed VLPs possess higher α-helix content, lower solvent-accessible surface area, and a more compact conformation.
• VLPs exhibited reduced flexibility at 37°C due to inter-subunit conformational locking, a short-term anti-Arrhenius behavior.
• Vaccination with IBDV VLPs induced dose-dependent high antibody titers and conferred complete protection against IBDV challenge without bursal lesions.

Conclusions:

• The structural characteristics of IBDV VLPs contribute to their superior stability.
• IBDV VLPs represent a stable and effective vaccine candidate, offering complete protection.
• This study provides valuable insights into the structure-stability relationship of VLPs for future vaccine design.