Infectious bursal disease (IBD), caused by infectious bursal disease virus (IBDV), is an acute and highly contagious avian infection that primarily causes severe immunosuppression in chickens. Since the 1980s, very virulent IBDV (vvIBDV) has triggered a global crisis in the poultry industry due to its high mortality. Although IBD has become largely sporadic in recent years following widespread vaccination, the persistent threat of vvIBDV underscores the critical need for novel vaccines that are both safer and more effective. In this study, a lipid nanoparticle (LNP)-encapsulated DNA vaccine encoding the VP2 antigen of vvIBDV (pCAHLJVP2-LNP) was developed. Following in vitro characterization-including assessment of protein expression, particle size, polydispersity index, and encapsulation efficiency; we evaluated the immunogenicity and protective efficacy of the vaccine in specific pathogen-free (SPF) chickens using two immunization doses (10 or 20 μg) and two regimens (single or double immunization). The 20 μg dose elicited superior immune responses compared to the 10 μg dose. Notably, even a single immunization with 20 μg of pCAHLJVP2-LNP elicited specific neutralizing antibodies and conferred complete protection, preventing both bursal lesions and mortality in chickens after vvIBDV challenge. These findings demonstrate that pCAHLJVP2-LNP is a promising vaccine candidate capable of inducing comprehensive immune protection, highlighting its potential for clinical application in vvIBDV prevention.

Keywords: DNA vaccine; Infectious bursal disease (IBD); Lipid nanoparticle (LNP); VP2; Very virulent IBD virus (vvIBDV).