Plant Expression Systems for the Production of Vaccines

  • J. K.-C. Ma
  • N. D. Vine
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 236)


Plant biotechnology is a rapidly expanding area, and in the last 5–10 years it has become apparent that plant systems may be particularly valuable for the expression and production of recombinant molecules. A considerable effort has focused on genetic engineering for the improvement of plant characteristics and agricultural properties, but the technology has also been applied to the production of “high-value” products, namely pharmaceutical compounds and vaccines. A particular attraction of this approach is the potential for growing immunotherapeutic reagents on an agricultural scale, thereby significantly reducing the costs of production. However, as this review will attempt to demonstrate, there are many other advantages related to the use of plants. This chapter will review the major advances in plant genetic engineering for the production of products for both active and passive immunisation. It will discuss the advantages and disadvantages of the plant expression systems as well as strategies that have been devised to overcome some of the specific problems.


Transgenic Plant Tobacco Mosaic Virus Secretory Component Protein Disulphide Isomerase Tomato Bushy Stunt Virus 
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  1. Arakawa T, Chong DK, Merritt JL, Langridge WH (1997) Expression of cholera toxin B subunit oligomers in transgenic potato plants. Transgenic Res 6:403–413PubMedCrossRefGoogle Scholar
  2. Benvenuto E, Ordas RJ, Tavazza R, Ancora G, Biocca S, Cattaneo A, Galeffi P (1991) ‘Phytoantibodies’: a general vector for the expression of immunoglobulin domains in transgenic plants. Plant Mol Biol 17:865–874CrossRefGoogle Scholar
  3. Carrillo C, Wigdorovitz A, Oliveros JC, Zamorano PI, Gomez N, Salinas J, Escribano JM, Borca MV (1998) Protective immune response to foot-and-mouth disease virus with VP1 expressed in transgenic plants. J Virol 72:1688–1690PubMedGoogle Scholar
  4. Cruz SS, Chapman S, Roberts AG, Roberts IM, Prior DA (1996) Assembly and movement of a plant virus carrying a green fluorescent protein overcoat. Proc Natl Acad Sci USA 93:6286–6290PubMedCrossRefGoogle Scholar
  5. Curtiss R, Cardineau GA (1990) World Intellectual Property Organization PCT/US89/03799.Google Scholar
  6. Dalsgaard K, Uttenthal A, Jones TD, Xu F, Merryweather A, Hamilton WD, Boshuizen RS, Kamstrup S, Lomonossoff GP, Vela C, Casal JI, Meloen RH, Rodgers PB (1997) Plant-derived vaccine protects target animals against a viral disease. Nat Biotechnol 15:248–252PubMedCrossRefGoogle Scholar
  7. De Neve M, De Loose M, Jacobs A, Van Houdt H, Kaluza B, Weidle U, Depicker A (1993) Assembly of an antibody and its derived antibody fragment in Nicotiana and Arabidopsis. Transgenic Res 2:227–237PubMedCrossRefGoogle Scholar
  8. Della-Cioppa G, Grill LK (1996) Production of novel compounds in higher plants by transfection with RNA viral vectors. Ann N Y Acad Sci 792:57–61CrossRefGoogle Scholar
  9. Denecke J, Goldman MH, Demolder J, Seurinck J, Botterman J (1991) The tobacco luminal binding protein is encoded by a multigene family [published erratum appears in Plant Cell (1991) 3:1251]. Plant Cell 3:1025–1035PubMedCrossRefGoogle Scholar
  10. Domansky N, Ehsani P, Salmanian A-H, Medvedeva T (1995) Organ specific expression of hepatitis B surface antigen in potato. Biotechnol Lett 17:863–866CrossRefGoogle Scholar
  11. Donson J, Kearney CM, Hilf ME, Dawson WO (1991) Systemic expression of a bacterial gene by a tobacco mosaic virus-based vector. Proc Natl Acad Sci USA 88:7204–7208PubMedCrossRefGoogle Scholar
  12. During K, Hippe S, Kreuzaler F, Schell J (1990) Synthesis and self assembly of a functional antibody in transgenic Nicotiana tabacum. Plant Mol Biol 15:281–293PubMedCrossRefGoogle Scholar
  13. Ehsani P, Khabiri A, Domansky NN (1997) Polypeptides of hepatitis B surface antigen produced in transgenic potato. Gene 190:107–111PubMedCrossRefGoogle Scholar
  14. Faye L, Johnson KD, Sturm A, Chrispeels MJ (1989) Structure, biosynthesis and function of asparagine-linked glycans on plant glycoproteins. Physiol Plant 75:309–314CrossRefGoogle Scholar
  15. Fiedler U, Phillips J, Artsaenko O, Conrad U (1997) Optimization of scFv antibody production in transgenic plants. Immunotechnology 3:205–216PubMedCrossRefGoogle Scholar
  16. Fitchen J, Beachy RN, Hein MB (1995) Plant virus expressing hybrid coat protein with added murine epitope elicits autoantibody response. Vaccine 13:1051–1057PubMedCrossRefGoogle Scholar
  17. Fontes EBP, Shank BB, Wrobel RL, Moose SP, O’Brian GR, Wurtzel ET, Boston RS (1991) Characterization of an immunoglobulin binding-protein homolog in the maize floury-2 endosperm mutant. Plant Cell 3:483–496PubMedCrossRefGoogle Scholar
  18. Haq TA, Mason HS, Clements JD, Arntzen CJ (1995) Oral immunization with a recombinant bacterial antigen produced in transgenic plants (comments). Science 268:714–716PubMedCrossRefGoogle Scholar
  19. Haynes JR, Cunningham J, von Seefried A, Lennick M, Garvin RT, Shen S (1986) Development of a genetically engineered, candidate polio vaccine employing the self-assembling properties of the tobacco mosaic virus coat protein. Biotechnology 4:637–641CrossRefGoogle Scholar
  20. Hein MB, Tang Y, McLeod DA, Janda KD, Hiatt AC (1991) Evaluation of immunoglobulins from plant cells. Biotechnol Prog 7:455–461PubMedCrossRefGoogle Scholar
  21. Hiatt AC, Cafferkey R, Bowdish K (1989) Production of antibodies in transgenic plants. Nature 342:76–78PubMedCrossRefGoogle Scholar
  22. Joelson T, Akerblom L, Oxelfelt P, Strandberg B, Morris TJ (1997) Presentation of a foreign peptide on the surface of tomato bushy stunt virus. J Gen Virol 78:1213–1217PubMedGoogle Scholar
  23. Kumagai MH, Turpen TH, Weinzettl N, Della-Cioppa G, Turpen AM, Donson J, et al. (1993) Rapid, high-level expression of biologically active a-tricosanthin in transfected plants by an RNA viral vector. Proc Natl Acad Sci USA 90:427–430PubMedCrossRefGoogle Scholar
  24. Ma JK-C, Hunjan M, Smith R, Kelly C, Lehner T (1990) An investigation into the mechanism of protection by local passive immunisation with monoclonal antibodies against Streptococcus mutans. Infect Immun 58:3407–3414PubMedGoogle Scholar
  25. Ma JK-C, Lehner T, Stabila P, Fux CI, Hiatt A (1994) Assembly of monoclonal antibodies with IgGl and IgA heavy chain domains in transgenic tobacco plants. Eur J Immunol 24:131–138PubMedCrossRefGoogle Scholar
  26. Ma JK-C, Hiatt A, Hein MB, Vine N, Wang F, Stabila P, van Dolleweerd C, Mostov K, Lehner T (1995) Generation and assembly of secretory antibodies in plants. Science 268:716–719PubMedCrossRefGoogle Scholar
  27. Ma SW, Zhao DL, Yin ZQ, Mukherjee R, Singh B, Qin HY, Stiller CR (1997) Transgenic plants expressing autoantigens fed to mice to induce oral immune tolerance. Nat Med 3:793–796PubMedCrossRefGoogle Scholar
  28. Ma JK-C, Hikmat BY, Wycoff K, Vine N, Chargelegue D, Yu L, Hein MB, Lehner T (1998) Characterization of a recombinant plant monoclonal secretory antibody and preventive immunotherapy in humans. Nat Med 4:(in press)Google Scholar
  29. Mason HS, Lam DM, Arntzen CJ (1992) Expression of hepatitis B surface antigen in transgenic plants. Proc Natl Acad Sci USA 89:11745–11749PubMedCrossRefGoogle Scholar
  30. Mason HS, Ball JM, Shi JJ, Jiang X, Estes MK, Arntzen CJ (1996) Expression of Norwalk virus capsid protein in transgenic tobacco and potato and its oral immunogenicity in mice. Proc Natl Acad Sci USA 93:5335–5340PubMedCrossRefGoogle Scholar
  31. McGarvey PB, Hammond J, Dienelt MM, Hooper C, Fu Z-F, Dietzschold B, Koprowski H, Michaels FH (1995) Expression of the rabies virus glycoprotein in transgenic tomatoes. Biotechnology 13:1484—1487PubMedGoogle Scholar
  32. McLain L, Durrani Z, Wisniewski LA, Porta C, Lomonossoff GP., Dimmock NJ (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 14:799–810PubMedCrossRefGoogle Scholar
  33. Mestecky J, McGhee JR (1987) Immunoglobulin A (IgA): molecular and cellular interactions involved in IgA biosynthesis and immune response. Adv Immunol 40:153–245PubMedCrossRefGoogle Scholar
  34. Owen M, Gandecha A, Cockburn B, Whitelam G (1992) Synthesis of a functional anti-phytochrome single chain Fv protein in transgenic tobacco. Biotech 10:790–794CrossRefGoogle Scholar
  35. Porta C, Spall VE, Loveland J, Johnson JE, Barker PJ (1994) Development of cowpea mosaic virus as a high-yielding system for the presentation of foreign peptides. Virology 202:949–955PubMedCrossRefGoogle Scholar
  36. Porta C, Lomonossoff GP (1996) Use of viral replicons for the expression of genes in plants (review) [73 refs]. Mol Biotechnol 5:209–221PubMedCrossRefGoogle Scholar
  37. Schouten A, Roosien J, van Engelen FA, de Jong GAM, Borst-Vrenssen AWM, Zilverentant JF, Bosch D, Stiekema WJ, Gommers FJ, Schots A, Bakker J (1996) The C-terminal KDEL sequence increases the expression level of a single-chain antibody designed to be targeted to both the cytosol and the secretory pathway in transgenic tobacco. Plant Mol Biol 30:781–793PubMedCrossRefGoogle Scholar
  38. Sturm A, Van Kuik JA, Vliegenthart JF, Chrispeels MJ (1987) Structure, position, and biosynthesis of the high mannose and the complex oligosaccharide side chains of the bean storage protein phaseolin. J Biol Chem 262:13392–13403PubMedGoogle Scholar
  39. Sugiyama Y, Hamamoto H, Takemoto S, Watanabe Y, Okada Y (1995) Systemic production of foreign peptides on the particle surface of tobacco mosaic virus. FEBS Lett 359:247–250PubMedCrossRefGoogle Scholar
  40. Thanavala Y, Yang YF, Lyons P, Mason HS, Arntzen C (1995) Immunogenicity of transgenic plant-derived hepatitis B surface antigen. Proc Natl Acad Sci USA 92:3358–3361PubMedCrossRefGoogle Scholar
  41. Turpen TH, Reinl SJ, Charoenvit Y, Hoffman SL, Fallarme V, Grill LK (1995) Malarial epitopes expressed on the surface of recombinant tobacco mosaic virus. Biotechnology 13:53–57PubMedCrossRefGoogle Scholar
  42. Usha R, Rohll JB, Spall VE, Shanks M, Maule AJ, Johnson JE (1993) Expression of an animal virus antigenic site on the surface of a plant virus particle. Virology 197:366–374PubMedCrossRefGoogle Scholar
  43. van Engelen FA, Schouten A, Molthoff JW, Roosien J, Salinas J, Dirkse W, Schots A, Bakker J, Gommers FJ, Jongsma MA, et al. (1994) Coordinate expression of antibody subunit genes yields high levels of functional antibodies in roots of transgenic tobacco. Plant Mol Biol 26:1701–1710PubMedCrossRefGoogle Scholar
  44. von Schaewen A, Sturm A, O’Neill J, Chrispeels MJ (1993) Isolation of a mutant arabidopsis plant that lacks N-acetyl glucosaminyl transferase I and is unable to synthesise Golgi-modified complex N-linked glycans. Plant Physiol 102:1109–1118CrossRefGoogle Scholar
  45. Yusibov V, Modelska A, Steplewski K, Agadjanyan M, Hooper DC, Koprowski H (1997) Antigens produced in plants by infection with chimeric plant viruses immunize against rabies virus and HIV-1. Proc Natl Acad Sci USA 94:5784–5788PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • J. K.-C. Ma
    • 1
  • N. D. Vine
    • 1
  1. 1.Unit of Immunology, Department of Oral Medicine and Pathology, 28th Floor, Guy’s TowerUMDS Guy’s HospitalLondonUK

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