Full text in pdf format
Production of recombinantantigens in plants for animal andhuman immunization - a review
Ekkehard Hansen
Laboratório de Biotecnologia, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense (UENF), Avenida Alberto Lamego, 2000, 28015-620 Campos dos Goytacazes, RJ, Brasil. Tel.: 024-7263764, Fax: 024-7263720, E-mail: ekki@uenf.br.
ABSTRACT
Plants present a cost effective production system for high value proteins. There is an increasing world demand for cheap vaccines that can be readily administered to the population, especially in economically less developed regions. A promising concept is the production of vaccines in plants that could be grown locally. Expression of antigenic peptides in the palatable parts of plants can lead to the production of edible active vaccines. Two major strategies are: i) to express antigens in transgenic plants, and ii) to produce antigenic peptides on the surface of plant viruses that could be used to infect host plants. This review considers the experimental data and early results for both strategies, and discusses the potential and problems of this new technology.
Keywords: antigens; plants; human immunization.
REFERENCES
Abler, M.L. and Green, P.J. (1996). Control of mRNA stability in higher plants. Plant Mol. Biol. 32: 63-78.
Beachy, R.N., Fitchen, J.H. and Hein, M.B. (1996). Use of plant viruses for delivery of vaccine epitopes. Ann. N. Y. Acad. Sci. 792: 43-49.
Bergmann, K.C. and Waldman, R.H. (1988). Stimulation of secretory antibody following oral administration of antigen. Rev. Infect. Dis. 10: 939-950.
Challacombe, S.J. and Tomasi, T.J. (1980). Systematic tolerance and secretory immunity after oral immunization. J. Exp. Med. 152: 1459-1472.
Chinn, A.M., Payne, S.R. and Comal, L. (1996). Variegation and silencing of the Heat Shock Cognate 80 gene are relieved by a bipartite downstream regulatory element. Plant J. 9: 325-339.
Dalsgaard, K., Uttenthal, A., Jones, T.D., Xu, F., Merrywheather, A., Hamilton, W.D.O., Langeveld, J.P.M., Boshuizen, R.S., Kamstrup, S., Lomonossoff, G.P., Porta, C., Vela, C., Casal, J.I., Meloen, R.H. and Rodgers, P.B. (1997). Plant-derived vaccine protects target animals against a viral disease. Nat. Biotechnol. 15: 248-252.
Dean, C., Favreau, M., Bond-Nutter, D., Bedbrook, J. and Dunsmuir, P. (1989). Sequences downstream of translation start regulate quantitative expression of two Petunia rbcS genes. Plant Cell 1: 201-208.
Dietrich, R.A., Radke, S.E. and Harada, J.J. (1992). Downstream DNA sequences are required to activate a gene expressed in the root cortex of embryos and seedlings. Plant Cell 4: 1371-1382.
Douglas, C.J., Hauffe, K.D., Ites-Morales, M., Ellard, M., Paskowski, U., Hahlbrock, K. and Dangl, J.L. (1991). Exonic sequences are required for elicitor and light activation of a plant defense gene, but promoter sequences are sufficient for tissue specific expression. EMBO J. 10: 1767-1775.
During, K., Hippe, S., Kreuzaler, F. and Schell, J. (1990). Synthesis and selfassembly of a functional monoclonal antibody in transgenic Nicotiana tabacum. Plant Mol. Biol. 15: 281-293.
Elliot, R.C., Dickey, L.F, White, M.J. and Thompson, W.F. (1989). cis-acting elements for light regulation of pea ferredoxin I gene expression are located within transcribed sequences. Plant Cell 1: 691-698.
Elson, C.O. and Ealding, W. (1984a). Generalized systemic and mucosal immunity in mice after mucosal stimulation with cholera toxin. J. Immunol. 132: 2736-2741.
Elson, C.O. and Ealding, W. (1984b). Cholera toxin feeding did not induce oral tolerance in mice and abrogated oral tolerance to an unrelated protein antigen. J. Immunol. 133: 2892-2897.
Ernst, P.B., Sicchitano, R., Underdown, B.J. and Bienenstock, J. (1988). Oral immunization and tolerance. In: Immunology of the Gastrointestinal Tract and Liver (M.F. Heyworth, M.F. and Jones, A.L., eds.). Raven Press, New York, pp. 125-144.
Fitchen, J., Beachy, R.N. and Hein, M.B. (1995). Plant virus expressing hybrid coat protein with added murine epitope elicits autoantibody response. Vaccine 13: 10511057.
Fox, J.L. (1996). WHO and UNICEF find vaccines too costly. Nat. Biotechnol. 14: 1532.
Hajishengallis, G.S., Hollingshead, S.K., Koga, T. and Russell, M.W. (1995). Mucosal immunization with a bacterial protein antigen genetically coupled to cholera toxin A2/B subunits. J. Immunol. 154: 4322-4332.
Hansen, E. and Harper, G. (Eds.) (1997). Differentially Expressed Genes in Plants - A Bench Manual. Taylor and Francis, London.
Haq, T.A., Mason, H.S., Clements, J.D. and Arntzen, C.J. (1995). Oral immunization with a recombinant bacterial antigen produced in transgenic plants. Science 268: 714-716.
Hein, M.B., Yeo, T.-C., Wang, F. and Sturtevant, A. (1996). Expression of cholera toxin subunits in plants. Ann. N. Y. Acad. Sci. 792: 50-56.
Hiatt, A.C. (1990). Antibodies produced in plants. Nature 344: 469-470.
Hiatt, A.C., Cafferkey, R. and Bowdish, K. (1989). Production of antibodies in transgenic plants. Nature 342: 76-78.
Hooper, D.C., Pierard, I., Modelska, A., Otvos, L., Fu, Z.F., Koprowski, H. and Dietzschold, B. (1994). Rabies ribonucleocapsid as an oral immunogen and immunological enhancer. Proc. Natl. Acad. Sci. USA 91: 10908-10912.
Jertbom, M., Svennerholm, A.-M. and Holmgren, J. (1992). Safety and immunogenicity of an oral recombinant cholera B subunit-whole cell vaccine in Swedish volunteers. Vaccine 10: 130-132.
Jobling, M.G. and Holmes, R.K. (1992). Fusion proteins containing the A2 domain of cholera toxin assemble with B polypeptides of cholera toxin to form immunoreactive and functional holotoxin-like chimeras. Infect. Immun. 60: 4915-4924.
Johnson, E. (1996). Edible plant vaccines (Editorial). Nat. Biotechnol. 14: 1532-1533.
Jorgensen, R.B., Hauser, T., Mikkelsen, T.R. and Ostergârd, H. (1996). Transfer of engineered genes from crops to wild plants. Trends Plant Sci. 1: 356-358.
Koziel, M.G., Carozzi, N.B. and Desai, N. (1996). Optimizing expression of transgenes with an emphasis on post-transcriptional events. Plant Mol. Biol. 32: 393-405.
Lindsey, K. (1996). Plant transformation systems. In: Transgenic Plants: A Production System for Industrial and Pharmaceutical Proteins (Owen, M.R.L. and Pen, J., eds.). John Wiley & Sons, Chichester, pp. 5-26.
Ma, J.K.-C. and Hiatt, A. (1996). Expressing antibodies in plants for immunotherapy. In: Transgenic Plants: A Production System for Industrial and Pharmaceutical Proteins (Owen, M.R.L. and Pen, J., eds.). John Wiley & Sons, Chichester, pp. 229-243.
Ma, J.K.-C., Hiatt, A., Hein, M.B., Vine, N.D., Wang, F., Stabila, P., Van Dolleweerd, C., Mostov, K. and Lehner, T. (1995). Generation and assembly of secretory antibodies in plants. Science 268: 716-719.
Mariani, C.; De Beuckeleer, M., Truettner, J., Leemans, J. and Goldberg, R.B. (1990). Induction of male sterility in plants by a chimaeric ribonuclease gene. Nature 347: 737-741.
Mariani, C., Gossele, V., De Beuckeleer, M., De Block, M., Goldberg, R.B., De Greef, W. and Leemans, J. (1992). A chimaeric ribonuclease-inhibitor gene restores fertility to male sterile plants. Nature 357: 384-387.
Mason, H.S., Lam, D.M.-K. and Arntzen, J. (1992). Expression of hepatitis B surface antigen in transgenic plants. Proc. Natl. Acad. Sci. USA 89: 11745-11749.
Mason, H.S., Ball, M., Shi, X., Estes, M.K. and Arntzen, C.J. (1996). 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.
Matzke, M. and Matzke, A. (1995). How and why do plants inactivate homologous (trans) genes? Plant Physiol. 107: 679-685.
Matzke, M.A., Primig, M., Trnovsky, J. and Matzke, A.J.M. (1989). Reversible methylation and inactivation of marker genes in sequentially transformed tobacco plants. EMBO J. 8: 643-649.
McGarvey, P.B., Hammond, J., Dienelt, M.M., Hooper, D.C., Fu, Z.F., Dietzschold, B., Koprowski, H. and Michaels, F.H. (1995). Expression of the rabies virus glycoprotein in transgenic tomatoes. Bio/Technol. 13: 1484-1487.
McLain, L. and Dimmock, N.J. (1994). Single- and multi-hit kinetics of IgG-neutralization of human immunodeficiency virus type 1 by monoclonal antibodies. J. Gen. Virol. 75: 1457-1460.
McLain, L., Porta, C., Lomonossoff, G.P., Durrani, Z. and Dimmock, N.J. (1995). Human immunodeficiency virus type-1 neutralizing antibodies raised to a glycoprotein 41 peptide expressed on the surface of a plant virus. AIDS Res. Hum. Retroviruses 11: 327-334.
McLain, L., Durrani, Z., Wisniewski, L.A., Porta, C., Lomonossoff, G.P. and Dimmock, N.J. (1996). Stimulation of neutralizing antibodies to human immunodeficiency virus type 1 in three strains of mice immunized with a 22 amino acid peptide of gp41 expressed on the surface of a plant virus. Vaccine 14: 799-810.
Mekalanos, J.J, Swartz, D.J., Pearson, G.D.N., Harford, N.,Groyne, F. and De Wilde, M. (1983). Cholera toxin genes: Nucleotide sequence, deletion analysis and vaccine development. Nature 306: 551-557.
Meyer, P. (1995). Understanding and controlling transgene expression. Trends Biotechnol. 13: 332-337.
Miele, L. (1997). Plants as bioreactors for biopharmaceuticals: regulatory considerations. Trends Biotechnol. 15: 45-50.
Millar, S.E., Chamow, S.M., Baur, A.W., Oliver, C., Robey, F. and Dean, J. (1989). Vaccination with a synthetic zona pellucida peptide produces long-term contraception in female mice. Science 246: 935-938.
Porta, C., Spall, V.E., Loveland, J., Johnson, J.E., Barker, P.J. and Lomonossoff, G.P. (1994). Development of cowpea mosaic virus as a high-yielding system for the presentation of foreign peptides. Virology 202: 949-955.
Richardson, J.H. and Marasco, W.A. (1995). Intracellular antibodies: development and therapeutic potential. Trends Biotechnol. 13: 306-310.
Ruedl, C. and Wolf, H. (1995). Features of oral immunization. Int. Arch. Allergy Appl. Immunol. 108: 334-449.
Spangler, B.D. (1992). Structure and function of cholera toxin and the related Escherichia coli heat-labile enterotoxin. Microbiol. Rev. 56: 622-647.
Sun, J.B., Holmgren, J. and Czerkinsky, C. (1994). Cholera toxin B subunit, an efficient transmucosal carrier-delivery system for induction of peripheral immunological tolerance. Proc. Natl. Acad. Sci. USA 91: 1079510799.
Thanavala, Y., Yang, Y.-F., Lyons, P., Mason, H.S. and Arntzen, C. (1995). Immunogenicity of transgenic plant derived hepatitis B surface antigen. Proc. Natl. Acad. Sci. USA 92: 3358-3361.
Turpen, T.H., Reinl, S.J., Charoenvit, Y., Hoffman, S.L., Fallarme, V. and Grill, L.K. (1995). Malarial epitopes expressed on the surface of recombinant tobacco mosaic virus. Bio/Technol. 13: 53-57.
Usha, R., Rohll, J.B., Spall, V.E., Shanks, M., Maule, A.J.,Johnson, J.E. and Lomonossoff, G.P. (1993). Expression of an animal virus antigenic site on the surface of a plant virus particle. Virology 197: 366-374.