Production of hepatitis B surface antigen in transgenic plants for oral immunization

Here we present data showing oral immunogenicity of recombinant hepatitis B surface antigen (HBsAg) in preclinical animal trials. Mice fed transgenic HBsAS potato tubers showed a primary immune response (increases in HBsAg-sp ecific serum antibody) that could be greatly boosted by intraperitoneal del ivery of a single subimmunogenic dose of commercial HBsAS vaccine, indicati ng that plants expressing HBsAg in edible tissues may be a new means for or al hepatitis B immunization. However, attainment of such a goal will requir e higher HBsAS expression than was observed for the potatoes used in this s tudy. We conducted a systematic analysis of factors influencing the accumul ation of HBsAg in transgenic potato, including 5' and 3' flanking elements and protein targeting within plant cells. The most striking improvements re sulted from (1) alternative polyadenylation signals, and (2) fusion protein s containing targeting signals designed to enhance integration or retention of HBsAS in the endoplasmic reticulum (ER) of plant cells.