Purpose. DNA-based vaccines encoding viral antigens have been shown to elicit immune responses in animal models. In this study, a plasmid DNA (pDNA) coexpressing the middle envelope protein of hepatitis B virus (HBV) and Interleukin-2 (IL-2) was incorporated into Poly (D, L-lactic-co-glycolic acid) (PLGA) microspheres and three different formulations were investigated for their potential as a vaccine delivery system.