Infectious bursal disease (IBD) is an acute and contagious disease in young chickens known as Gumboro disease. This disease is characterized by the destruction of the lymphoid organs, in particular the bursa of Fabricious. It is one of the most important poultry viruses threatening the chicken industry worldwide.described in Europe at the end the 1980s, the acute forms of the disease were then described in Japan in the early 1990s, and they have rapidly spread all over Asia and to other major parts of the world. First The immunosuppressive effect of this virus leads to incomplete response to vaccination and secondary infections in the presence of other viruses or bacteria. The causative agent of the Gumboro disease, named as Infectious bursal disease virus (IBDV) belongs to the family Birnaviridae of the genus Avibirnavirus which is characterized by a bisegmented dsRNA genome. The larger segment A (approximately 3400 base pairs (bp)) contains two open reading frames (ORF). The larger ORF of segment A is monocistronic and encodes a polyporotein that is auto-processed after several steps into mature VP2, VP3 and VP4. Segment A can also encode VP5, a short 17 Kda protein, from a short, partially overlapping ORF. The smaller genom segment B (approximately 2500 bp) encodes VP1, the viral RNA polymerase of 90 KDa. The virion has a single capsid shell of icosahedral symmery composed of 32 capsomers and a diameter of 60 to 90 nm. The external surface of the virion is composed of trimeric subunits formed by VP2 and the inner capsid is built of trimeric subunits formed by VP3. Overcoming to the virus is difficult; therefore, vaccination of poultry farms is essential. At 1987, it caused heavy economical losses to the poultry industry due to the appearance of new strains and spreading the disease to the most parts of the world. Classic vaccines and maternally derived antibodies did not protect poultries against these new stains. Hence numerous studies have been performed to develop new generation vaccines especially by expression of VP2 protein in E. coli , bacteriophages, yeast, fowlpox virus and herpesvirus. VP2 has long been identified as the host-protective antigen as it contains the antigenic regions responsible for the induction of neutralizing antibodies. The epitopes recognized by neutralizing antibodies are conformational and have been mapped to amino acids 206-350 this region called as hypervariable region of VP2 (hvVP2). The aim of this study was the expression this region of VP2 gene in prokaryotic system ( E. coli ). Both natural and optimized coding sequences of the hvVP2 gene were cloned in pET26b plasmid and transformed into BL21 (DE3) strain. But the results showed low level of protein expression in both strategies. NusA and GST, when used as a fusion partners, improved the expression level of hvVP2. The fusion protein