Infectious bursal disease virus (IBDV) causes immunosuppression in poultry (3 to 6 weeks age), resulting in severe production and economic losses. Current vaccination strategies exploit live attenuated or killed vaccines based on classical virulent IBDV strains, which are proven to be ineffective against variant and/or very virulent (vv) strains -currently circulating in the field throughout the world. Keeping in view the urgent need of clean and cost-effective vaccines of high quality, we have engineered VP2 gene as host protective major antigen. The gene was synthesized to express in chloroplast genome, plastome. Sequence and structural characterization of synthetic gene and corresponding protein were carried out using a variety of molecular biology and bioinformatics tools. In silico physico-chemical analysis demonstrated that the synthetic VP2 was an acidic protein of 54KDa. Moreover, it was found to be highly thermo-stable with a computed instability index of 30.38 and hydrophobic in nature with GRAVY index of 0.115. The sequence analyses including phylogeny and multiple sequence alignment with representative classical, attenuated and vv IBDV strains from different regions of the world exhibited antigenic similarity with currently circulating vvIBDV strains and predicted its worldwide effectiveness as a subunit vaccine. The 3D structure prediction using I-TASSER server and surface representation of epitopic loops on VP2 trimer using UCSF Chimera software indicated the potential of synthetic VP2 as an antigenic protein. The generated information has paved the way for the functional characterization of synthetic protein as a subunit vaccine employing transgenic approaches in future. ©2018 PVJ. All rights reservedKey words: Infectious bursal disease virus Sequence analyses Structure analysis VP2 subunit vaccine To Cite This Article: Fayyaz M, Khan MS, Joyia FA and Zia MA, 2019. Sequence and structural analysis of synthetic VP2 antigenic protein as a subunit vaccine candidate against very virulent strains of infectious bursal disease virus. Pak Vet J, 39(1): 106-110. http://dx.