Nature Medicine
4, 607 - 609 (1998)
doi:10.1038/nm0598-607
Immunogenicity in humans of a recombinant bacterial antigen delivered in a transgenic potatoCarol O. Tacket1, Hugh S. Mason2, Genevieve Losonsky1, John D. Clements3, Myron M. Levine1
& Charles J. Arntzen2
1Center for Vaccine Development, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201. email: ctacket@umppal.ab.umd.edu
2Boyce Thompson Institute for Plant Research, Inc., Tower Road, Ithaca, New York 14853-1801
3Tulane University School of Medicine, Department of Microbiology and Immunology, 1430 Tulane Avenue, New Orleans, Louisiana 70112 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
- 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 | ISI | ChemPort |
- Tacket, C.O. .et al. Initial safety and immunogenicity studies of an oral recombinant adenohepatitis vaccine. Vaccine 10, 673−676 (1992). | Article | PubMed | ISI | ChemPort |
- 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). | PubMed | ISI | ChemPort |
- 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).
- 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). | PubMed | ChemPort |
- 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). | PubMed | ChemPort |
- 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). | PubMed | ISI | ChemPort |
- 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).
- 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). | PubMed | ISI | ChemPort |
- 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 | PubMed | ChemPort |
- Sixma, T.K. et al. Crystal structure of a cholera toxin-related heat-labile enterotoxin from E. coli. Nature 351, 371−377 (1991). | Article | PubMed | ISI | ChemPort |
- 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 | ISI | ChemPort |
- 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). | ChemPort |
- 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).
- Sack, D.A. & Sack, R.B. Test for enterotoxigenic Escherichia coli using Yl adrenal cells in miniculture. Infect. Immun. 11, 334 (1975). | PubMed | ISI | ChemPort |
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