The extraordinary immunogenicity of the envelope protein of Hepatitis B virus (HBsAg) has been exploited to derive the pan-global vaccine to prevent Hepatitis B virus infection. HBsAg protein molecules spontaneously associate within a bipid layer to form empty virus-like particles (VLPs). Here we discuss ways in which HBsAg can be genetically engineered to derive recombinant DNA or VLP vaccines for pathogen associated diseases and some tumors which depend upon the adaptive immune response for prevention or resolution.