The novel variant infectious bursal disease virus (nVarIBDV) has emerged as a significant threat to the poultry industry because it causes severe damage to the bursa of Fabricius. Moreover, due to its antigenic variation, currently available commercial IBDV vaccines are unable to provide complete protection against it. To address this challenge, we constructed a recombinant virus rMDV-varVP2, which expresses the VP2 gene of nVarIBDV using the Marek's disease virus type 1 (MDV1) vaccine strain as the backbone for its persistence, with the aim of achieving effective control against nVarIBDV. The recombinant virus was successfully rescued and confirmed by cytopathic effect observation, electron microscopy, PCR, and sequencing. Western blotting and immunofluorescence assays verified expression of the exogenous varVP2 protein. rMDV-varVP2 maintained stable VP2 insertion and expression through at least 20 serial passages and showed replication kinetics comparable to those of the parental rMSΔMeq strain in vitro. In specific-pathogen-free chickens, rMDV-varVP2 induced both humoral and cellular immune responses, including ELISA-detectable anti-VP2 antibodies, nVarIBDV-neutralizing antibodies, increased IFN-γ-secreting cells, and upregulated cytokine expression. After challenge with nVarIBDV SHG19 strain, vaccinated chickens were protected from bursal atrophy and histopathological damage, with significantly reduced viral loads in the bursa of Fabricius. These results demonstrate that rMDV-varVP2 provides effective protection against nVarIBDV challenge and represents a promising MDV1-vectored vaccine strategy for controlling nVarIBDV in poultry.

Keywords: Infectious bursal disease virus; Marek's disease virus; Novel variant strains; Protective efficacy; Recombinant virus.