A bio-nanocapsule containing envelope (E) protein domain III of Japanese encephalitis virus (JEV) protects mice against lethal JEV infection.

An engineered bio-nanocapsule (BNC), comprising modified hepatitis B surface antigen L protein, was used as a physical scaffold for envelope (E) protein domain III (D3) of Japanese encephalitis virus (JEV). At the N-terminus, the BNC contained a two-tandem repeat of the Z domain (ZZ) derived from Staphylococcus aureus protein A (ZZ-BNC). The lysine-rich ZZ moiety exposed on the surface of ZZ-BNC was used for chemical conjugation with the JEV D3 antigen, which was expressed and purified from Escherichia coli. Immunization of mice with D3 loaded on the surface of ZZ-BNC (ZZ-BNC:D3) augmented serum IgG responses against JEV, and conferred increased protection against lethal JEV infection. These results suggest that the surface display of weakly immunogenic inert recombinant antigens, which by themselves cannot form virus-like particles, can be transformed to immunogenic antigens by the exploitation of ZZ-BNC.