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 HBsAg potato tubers showed a primary immune response (increases in HBsAg-specific serum antibody) that could be greatly boosted by intraperitoneal delivery of a single subimmunogenic dose of commercial HBsAg vaccine, indicating that plants expressing HBsAg in edible tissues may be a new means for oral hepatitis B immunization. However, attainment of such a goal will require higher HBsAg expression than was observed for the potatoes used in this study. We conducted a systematic analysis of factors influencing the accumulation of HBsAg in transgenic potato, including 5' and 3' flanking elements and protein targeting within plant cells. The most striking improvements resulted from (1) alternative polyadenylation signals, and (2) fusion proteins containing targeting signals designed to enhance integration or retention of HBsAg in the endoplasmic reticulum (ER) of plant cells.
Richter
L J
LJ
Boyce Thompson Institute for Plant Research Inc., Tower Rd., Ithaca, NY 14853-1801, USA.
Thanavala
Y
Y
Arntzen
C J
CJ
Mason
H S
HS
D000284:Administration, Oral; D000818:Animals; D015152:Blotting, Northern; D002772:Cholera Toxin / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006509:Hepatitis B / Q000276:immunology / Q000517:prevention & control*; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D030821:Plants, Genetically Modified; D010947:Plants, Toxic; D010957:Plasmids / Q000378:metabolism; D018087:Plastids / Q000378:metabolism; D011061:Poly A / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D011198:Solanum tuberosum / Q000235:genetics; D013997:Time Factors; D014026:Nicotiana / Q000235:genetics; D014170:Transformation, Genetic; D014612:Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*
D006514:Hepatitis B Surface Antigens; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D014612:Vaccines; D011061:Poly A; D002772:Cholera Toxin