Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Immunogenicity in humans of a recombinant bacterial antigen delivered in a transgenic potato

Abstract

Compared with vaccine delivery by injection, oral vaccines offer the hope of more convenient immunization strategies and a more practical means of implementing universal vaccination programs throughout the world. Oral vaccines act by stimulating the immune system at effector sites (lymphoid tissue) located in the gut. Genetic engineering has been used with variable success to design living and non-living systems as a means to deliver antigens to these sites and to stimulate a desired immune response1–4. More recently, plant biotechnology techniques have been used to create plants which contain a gene derived from a human pathogen; the resultant plant tissues will accumulate an antigenic protein encoded by the foreign DNA5–10. In pre-clinical trials, we found that antigenic proteins produced in transgenic plants retained immunogenic properties when purified; if injected into mice the antigen caused production of protein-specific antibodies6. Moreover, in some experiments, if the plant tissues were simply fed to mice, a mucosal immune response occurred7–10. The present study was conducted as a proof of principle to determine if humans would also develop a serum and/or mucosal immune response to an antigen delivered in an uncooked foodstuff.

References

  1. Tacket, C.O. et al. Comparison of the safety and immunogenicity of aroC aroD and cya crp Salmonella typhi strains in adult volunteers. Infect. Immun. 60, 536–541 (1992).

    PubMed  PubMed Central  CAS  Google Scholar 

  2. Tacket, C.O. .et al. Initial safety and immunogenicity studies of an oral recombinant adenohepatitis vaccine. Vaccine 10, 673–676 (1992).

    Article  CAS  Google Scholar 

  3. Tacket, C.O. .et al. Enteral immunization and challenge of volunteers given enterotoxigenic E. coli CFA/II encapsulated in biodegradable microspheres. Vaccine 12, 1270–1274 (1994).

    Article  CAS  Google Scholar 

  4. Edelman, R. In: New Generation Vaccines, 2nd Edn (eds Levine M. M., Woodrow G.C., Kaper J.B., Cobon G.S.) 173–192 (Marcel Dekker, New York, 1997).

  5. Mason, H.S., Lam, D.M-K. & Arntzen, C. Expression of hepatitis B surface antigen in transgenic plants. Proc. Natl. Acad. Sci. USA 89, 11745–11749 (1992).

    Article  CAS  Google Scholar 

  6. Thanavala, Y., Yang, Y.-F., Lyons, P., Mason, H.S. & Arntzen, C. Immunogenicity of transgenic plant-derived hepatitis B surface antigen. Proc. Natl. Acad. Sci. USA 92, 3358–3361 (1995).

    Article  CAS  Google Scholar 

  7. Haq, T.A., Mason, H.S., Clements, J.D. & Arntzen, C.J. Oral immunization with a recombinant bacterial antigen produced in transgenic plants. Science 268, 714–716 (1995).

    Article  CAS  Google Scholar 

  8. Mason, H.S., Haq, T.A., Clements, J.D. & Arntzen, C.J. Edible vaccine protects mice against E. coli heat-labile enterotoxin (LT): potatoes expressing a synthetic LT-B gene. Vaccine (in the press).

  9. Arakawa, T., Chong, D.K.X. & Langridge, W.H.R. Efficacy of a food plant-based oral cholera toxin B subunit vaccine. Nature Biotech. 16, 292–297 (1998).

    Article  CAS  Google Scholar 

  10. Mason, H.S. et al. Expression of Norwalk virus capsid protein in transgenic tobacco and potato and its oral immunogenicity in mice. Proc. Natl. Acad. Sci. USA 93, 5335–5340 (1996).

    Article  CAS  Google Scholar 

  11. Sixma, T.K. et al. Crystal structure of a cholera toxin-related heat-labile enterotoxin from E. coli . Nature 351, 371–377 (1991).

    Article  CAS  Google Scholar 

  12. Black, R.E. et al. Protective efficacy in humans of killed whole-vibrio oral cholera vaccine with and without the B subunit of cholera toxin. Infect. Immun. 55, 1116–1120 (1987).

    PubMed  PubMed Central  CAS  Google Scholar 

  13. Van de Verg, L. et al. Specific immunoglobulin A-secreting cells in peripheral blood of humans following oral immunization with a bivalent Salmonella typhi-Shigella sonnei vaccine or infection by pathogenic S. sonnet. Infect. Immun. 58, 2002–2004 (1990).

    CAS  Google Scholar 

  14. Levine, M.M., Young, C.R., Black, R.E., Takeda, Y. & Finkelstein, R.A. Enzyme-linked immunosorbent assay to measure antibodies to purified heat-labile enterotoxins from human and porcine strains of Escherichia coli and to cholera toxin: application in serodiagnosis and seroepidemiology. J. Clin. Microbiol. 21, 174–179 (1995).

    Google Scholar 

  15. Sack, D.A. & Sack, R.B. Test for enterotoxigenic Escherichia coli using Yl adrenal cells in miniculture. Infect. Immun. 11, 334 (1975).

    PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Tacket, C., Mason, H., Losonsky, G. et al. Immunogenicity in humans of a recombinant bacterial antigen delivered in a transgenic potato. Nat Med 4, 607–609 (1998). https://doi.org/10.1038/nm0598-607

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm0598-607

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing