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

Liz J. Richter, Yasmin Thanavala, Charles J. Arntzen, Hugh S. Mason

Research output: Contribution to journalArticle

365 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1167-1171
Number of pages5
JournalNature biotechnology
Volume18
Issue number11
DOIs
StatePublished - Nov 20 2000

Keywords

  • Edible vaccine
  • Hepatitis B surface antigen
  • Oral vaccine
  • Potato
  • Protein engineering
  • Transgenic plants

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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