Transgenic Research

, Volume 16, Issue 3, pp 315–332 | Cite as

Production of vaccines and therapeutic antibodies for veterinary applications in transgenic plants: an overview

  • Doreen Manuela Floss
  • Dieter Falkenburg
  • Udo Conrad
Review

Abstract

During the past two decades, antibodies, antibody derivatives and vaccines have been developed for therapeutic and diagnostic applications in human and veterinary medicine. Numerous species of dicot and monocot plants have been genetically modified to produce antibodies or vaccines, and a number of diverse transformation methods and strategies to enhance the accumulation of the pharmaceutical proteins are now available. Veterinary applications are the specific focus of this article, in particular for pathogenic viruses, bacteria and eukaryotic parasites. We focus on the advantages and remaining challenges of plant-based therapeutic proteins for veterinary applications with emphasis on expression platforms, technologies and economic considerations.

Keywords

Molecular pharming Plant-based vaccines Therapeutic antibodies Transgenic plants Veterinary medicine 

Notes

Acknowledgements

We wish to thank our colleagues in the Phama-Planta consortium for helpful discussions.

References

  1. Alamillo JM, Monger W, Sola I, Garcia B, Perrin Y, Bestagno M, Burrone OR, Sabella P, Plana-Duran J, Enjuanes L, Lomonossoff GP, Garcia JA (2006) Use of virus vectors for the expression in plants of active full-length and single chain anti-coronavirus antibodies. Biotechnol J 1:1103–1111PubMedGoogle Scholar
  2. Almquist KC, McLean MD, Niu YQ, Byrne G, Olea-Popelka FC, Murrant C, Barclay J, Hall JC (2006) Expression of an anti-botulinum toxin A neutralizing single chain Fv recombinant antibody in transgenic tobacco. Vaccine 24:2079–2086PubMedGoogle Scholar
  3. Andre FE (2003) Vaccinology: past achievements, present roadblocks and future promises. Vaccine 21:593–595PubMedGoogle Scholar
  4. Ashraf S, Singh PK, Yadav DK, Shahnawaz M, Mishra S, Sawant SV, Tuli R (2005) High level expression of surface glycoprotein of Rabies Virus in tobacco leaves and its immunoprotective activity in mice. J Biotechnol 119:1–14PubMedGoogle Scholar
  5. Aziz MA, Sikriwal D, Singh S, Jarugula S, Kumar PA, Bhatnagar R (2005) Transformation of an edible crop with the pagA gene of Bacillus anthracis. FASEB J 19:1501–1503PubMedGoogle Scholar
  6. Bae JL, Lee JG, Kang TJ, Jang HS, Jang YS, Yang MS (2003) Induction of antigen-specific systemic and mucosal immune responses by feeding animals transgenic plants expressing the antigen. Vaccine 21:4052–4058PubMedGoogle Scholar
  7. Behring E and Kitasato S (1890) Ueber das Zustandekommen der Diphtherieimmunität und der Tetanusimmunität bei Tieren. Dtsch Med Wochenschr 16:1113–1114CrossRefGoogle Scholar
  8. Berinstein A, Vazquez-Rovere C, Asurmendi S, Gomez E, Zanetti F, Zabal O, Tozzini A, Grand DC, Taboga O, Calamante G, Barrios H, Hopp E, Carrillo E (2005) Mucosal and systemic immunization elicited by Newcastle Disease Virus (NDV) transgenic plants as antigens. Vaccine 23:5583–5589PubMedGoogle Scholar
  9. Birch-Machin I, Newell CA, Hibberd JM, Gray JC (2004) Accumulation of Rotavirus VP6 protein in chloroplasts of transplastomic tobacco is limited by protein stability. Plant Biotechnol J 2:261–270PubMedGoogle Scholar
  10. Boder ET, Midelfort KS, Wittrup KD (2000) Directed evolution of antibody fragments with monovalent femtomolar antigen-binding affinity. Proc Natl Acad Sci USA 97:10701–10705PubMedGoogle Scholar
  11. Brodzik R, Bandurska K, Deka D, Golovkin M, Koprowski H (2005) Advances in Alfalfa Mosaic Virus-mediated expression of anthrax antigen in planta. Biochem Biophys Res Commun 338:717–722PubMedGoogle Scholar
  12. Carter PJ (2006) Potent antibody therapeutics by design. Nat Biotechnol 6:343–357Google Scholar
  13. Casadevall A (1998) Antibody-based therapies as anti-infective agents. Expert Opin Investig Drugs 7:307–321PubMedGoogle Scholar
  14. Chadd HE, Chamow SM (2001) Therapeutic antibody expression technology. Curr Opin Biotechnol 12:188–194PubMedGoogle Scholar
  15. Chikwamba R, Cunnick J, Hathaway D, McMurray J, Mason H, Wang K (2002) A functional antigen in a practical crop: LT-B producing maize protects mice against Escherichia coli heat labile enterotoxin (LT) and cholera toxin (CT). Transgenic Res 11:479–493PubMedGoogle Scholar
  16. Clemente M, Curilovic R, Sassone A, Zelada A, Ange SO, Mentaberry AN (2005) Production of the main surface antigen of Toxoplasma gondii in tobacco leaves and analysis of its antigenicity and immunogenicity. Mol Biotechnol 30:41–49PubMedGoogle Scholar
  17. Companjen AR, Florack DEA, Slootweg T, Borst JW, Rombout JHWM (2006) Improved uptake of plant-derived LTB-linked proteins in carp gut and induction of specific humoral immune responses upon infeed delivery. Fish Shellfish Immunol 21:251–260PubMedGoogle Scholar
  18. Curtiss RI, Cardineau CA (1990) Oral immunization by transgenic plants. WO90/02484Google Scholar
  19. Daniell H, Khan MS, Allison L (2002) Milestones in chloroplast genetic engineering: an environmentally friendly era in biotechnology. Trends Plant Sci 7:84–91PubMedGoogle Scholar
  20. De Jaeger G, Scheffer S, Jacobs A, Zambre M, Zobell O, Goossens A, Depicker A, Angenon G (2002) Boosting heterologous protein production in transgenic dicotyledonous seeds using Phaseolus vulgaris regulatory sequences. Nat Biotechnol 20:1265–1268PubMedGoogle Scholar
  21. Deng SJ, Mackenzie CR, Hirama T, Brousseau R, Lowary TL, Young NM, Bundle DR, Narang SA (1995) Basis for selection of improved carbohydrate-binding single chain antibodies from synthetic gene libraries. Proc Natl Acad Sci USA 92:4992–4996PubMedGoogle Scholar
  22. Dong JL, Liang BG, Jin YS, Zhang WJ, Wang T (2005) Oral immunization with pBsVP6-transgenic alfalfa protects mice against Rotavirus infection. Virology 339:153–163PubMedGoogle Scholar
  23. Dus Santos MJ, Carrillo C, Ardila F, Rios RD, Franzone P, Piccone ME, Wigdorovitz A, Borca MV (2005) Development of transgenic alfalfa plants containing the Foot-and-Mouth-Disease Virus structural polyprotein gene P1 and its utilization as an experimental immunogen. Vaccine 23:1838–1843PubMedGoogle Scholar
  24. Dus Santos MJ, Wigdorovitz A (2005) Transgenic plants for the production of veterinary vaccines. Immunol Cell Biol 83:229–238PubMedGoogle Scholar
  25. Ehrlich P (1900) On immunity, with special reference to cell life. The Croonian lecture. Proc R Soc 66:424–448CrossRefGoogle Scholar
  26. Enjuanes L, van der Zeijst BAM (1995) Molecular basis of TGE coronavirus epidemiology. In: Siddell SG (ed) The Coronaviridae. Plenum Press, New YorkGoogle Scholar
  27. Fiedler U, Conrad U (1995) High-level production and long-term storage of engineered antibodies in transgenic tobacco seeds. Biotechnology 13:1090–1093PubMedGoogle Scholar
  28. Fischer R, Schillberg S (eds) (2004) Molecular farming – plant-made pharmaceuticals and technical proteins. WILEY-VCH Verlag GmbH & Co. KGaA, WeinheimGoogle Scholar
  29. Fischer R, Stoger E, Schillberg S, Christou P, Twyman RM (2004) Plant-based production of biopharmaceuticals. Curr Opin Plant Biol 7:152–158PubMedGoogle Scholar
  30. Fraley RT, Rogers SG, Horsch RB, Sanders PR, Flick JS, Adams SP, Bittner ML, Brand LA, Fink CL, Fry JS, Galluppi GR, Goldberg SB, Hoffmann NL, Woo SC (1983) Expression of bacterial genes in plant cells. Proc Natl Acad Sci USA 80:4803–4807PubMedGoogle Scholar
  31. Giddings G, Allison G, Brooks D, Carter A (2000) Transgenic plants as factories for biopharmaceuticals. Nat Biotechnol 18:1151–1155PubMedGoogle Scholar
  32. Gil F, Brun A, Wigdorovitz A, Catala R, Martinez-Torrecuadrada JL, Casal I, Salinas J, Borca MV, Escribano JM (2001) High-yield expression of a viral peptide vaccine in transgenic plants. FEBS Lett 488:13–17PubMedGoogle Scholar
  33. Gil F, Titarenko E, Terrada E, Arcalis E, Escribano JM (2006) Successful oral prime-immunization with VP60 from rabbit Haemorrhagic Disease Virus produced in transgenic plants using different fusion strategies. Plant Biotechnol J 4:135–143PubMedGoogle Scholar
  34. Guerrero-Andrade O, Loza-Rubio E, Olivera-Flores T, Fehervari-Bone T, Gomez-Lim MA (2006) Expression of the Newcastle Disease Virus fusion protein in transgenic maize and immunological studies. Transgenic Res 15:455–463PubMedGoogle Scholar
  35. Hanes J, Schaffitzel C, Knappik A, Pluckthun A (2000) Picomolar affinity antibodies from a fully synthetic naive library selected and evolved by ribosome display. Nat Biotechnol 18:1287–1292PubMedGoogle Scholar
  36. Hiatt A, Cafferkey R, Bowdish K (1989) Production of antibodies in transgenic plants. Nature 342:76–78PubMedGoogle Scholar
  37. Hood EE, Woodard SL, Horn ME (2002) Monoclonal antibody manufacturing in transgenic plants – myths and realities. Curr Opin Biotechnol 13:630–635PubMedGoogle Scholar
  38. Hoogenboom HR, de Bruine AP, Hufton SE, Hoet RM, Arends JW, Roovers RC (1998) Antibody phage display technology and its applications. Immunotechnology 4:1–20PubMedGoogle Scholar
  39. Horn ME, Woodard SL, Howard JA (2004) Plant molecular farming: systems and products. Plant Cell Rep 22:711–720PubMedGoogle Scholar
  40. Huang Y, Liang W, Pan A, Zhou Z, Huang C, Chen J, Zhang D (2003) Production of FaeG, the major subunit of K88 fimbriae, in transgenic tobacco plants and its immunogenicity in mice. Infect Immun 71:5436–5439PubMedGoogle Scholar
  41. Huang Y, Liang W, Wang Y, Zhou Z, Pan A, Yang X, Huang C, Chen J, Zhang D (2005) Immunogenicity of the epitope of the Foot-and-Mouth-Disease Virus fused with a hepatitis B core protein as expressed in transgenic tobacco. Viral Immunol 18:668–677PubMedGoogle Scholar
  42. Joensuu JJ (2006) Production of F4 fimbrial adhesin in plants: a model for oral porcine vaccine against enterotoxigenic Escherichia coli. Thesis/Dissertation. University of Helsinki, FinlandGoogle Scholar
  43. Joensuu JJ, Kotiaho M, Riipi T, Snoeck V, Palva ET, Teeri TH, Lang H, Cox E, Goddeeris BM, Niklander-Teeri V (2004) Fimbrial subunit protein FaeG expressed in transgenic tobacco inhibits the binding of F4ac enterotoxigenic Escherichia coli to porcine enterocytes. Transgenic Res 13:295–298PubMedGoogle Scholar
  44. Joensuu JJ, Kotiaho M, Teeri TH, Valmu L, Nuutila AM, Oksman-Caldentey KM, Niklander-Teeri V (2006a) Glycosylated F4 (K88) fimbrial adhesin FaeG expressed in barley endosperm induces ETEC-neutralizing antibodies in mice. Transgenic Res 15:359–373PubMedGoogle Scholar
  45. Joensuu JJ, Verdonck F, Ehrstrom A, Peltola M, Siljander-Rasi H, Nuutila AM, Oksman-Caldentey KM, Teeri TH, Cox E, Goddeeris BM, Niklander-Teeri V (2006b) F4 (K88) fimbrial adhesin FaeG expressed in alfalfa reduces F4+ enterotoxigenic Escherichia coli excretion in weaned piglets. Vaccine 24:2387–2394PubMedGoogle Scholar
  46. Kang TJ, Han SC, Jang MO, Kang KH, Jang YS, Yang MS (2004a) Enhanced expression of B-subunit of Escherichia coli heat-labile enterotoxin in tobacco by optimization of coding sequence. Appl Biochem Biotechnol 117:175–187PubMedGoogle Scholar
  47. Kang TJ, Han SC, Kim MY, Kim YS, Yang MS (2004b) Expression of non-toxic mutant of Escherichia coli heat-labile enterotoxin in tobacco chloroplasts. Protein Expr Purif 38:123–128PubMedGoogle Scholar
  48. Kang TJ, Han SC, Yang MS (2005a) Expression of the B subunit of E. coli heat-labile enterotoxin in tobacco using a herbicide resistance gene as a selection marker. Plant Cell Tissue Organ Cult 81:165–174Google Scholar
  49. Kang TJ, Kim YS, Jang YS, Yang MS (2005b) Expression of the synthetic neutralizing epitope gene of Porcine Epidemic Diarrhea Virus in tobacco plants without nicotine. Vaccine 23:2294–2297PubMedGoogle Scholar
  50. Kang TJ, Lee WS, Choi EG, Kim JW, Kim BG, Yang MS (2006) Mass production of somatic embryos expressing Escherichia coli heat-labile enterotoxin B subunit in Siberian ginseng. J Biotechnol 121:124–133PubMedGoogle Scholar
  51. Kang TJ, Loc NH, Jang MO, Jang YS, Kim YS, Seo JE, Yang MS (2003) Expression of the B subunit of E. coli heat-labile enterotoxin in the chloroplasts of plants and its characterization. Transgenic Res 12:683–691PubMedGoogle Scholar
  52. Kang TJ, Seo JE, Kim DH, Kim TG, Jang YS, Yang MS (2005c) Cloning and sequence analysis of the Korean strain of spike gene of Porcine Epidemic Diarrhea Virus and expression of its neutralizing epitope in plants. Protein Expr Purif 41:378–383PubMedGoogle Scholar
  53. Karaman S, Cunnick L, Wang K (2006) Analysis of immune response in young and aged mice vaccinated with corn-derived antigen against Escherichia coli heat-labile enterotoxin. Mol Biotechnol 32:31–42PubMedGoogle Scholar
  54. Khandelwal A, Lakshmi SG, Shaila MS (2003a) Expression of hemagglutinin protein of Rinderpest Virus in transgenic tobacco and immunogenicity of plant-derived protein in a mouse model. Virology 308:207–215PubMedGoogle Scholar
  55. Khandelwal A, Renukaradhya GJ, Rajasekhar M, Sita GL, Shaila MS (2004) Systemic and oral immunogenicity of hemagglutinin protein of Rinderpest Virus expressed by transgenic peanut plants in a mouse model. Virology 323:284–291PubMedGoogle Scholar
  56. Khandelwal A, Sita GL, Shaila MS (2003b) Oral immunization of cattle with hemagglutinin protein of Rinderpest Virus expressed in transgenic peanut induces specific immune responses. Vaccine 21:3282–3289PubMedGoogle Scholar
  57. Khandelwal A, Vally KJM, Geetha N, Venkatachalam P, Shaila MS, Sita GL (2003c) Engineering hemagglutinin (H) protein of Rinderpest Virus into peanut (Arachis hypogaea L.) as a possible source of vaccine. Plant Sci 165:77–84Google Scholar
  58. Kim TG, Kim MY, Kim BG, Kang TJ, Kim YS, Jang YS, Arntzen CJ, Yang MS (2007) Synthesis and assembly of Escherichia coli heat-labile enterotoxin B subunit in transgenic lettuce (Lactuca sativa). Protein Expr Purif 51:22–27PubMedGoogle Scholar
  59. Kim YS, Kang TJ, Jang YS, Yang MS (2005) Expression of neutralizing epitope of Porcine Epidemic Diarrhea Virus in potato plants. Plant Cell Tissue Organ Cult 82:125–130Google Scholar
  60. Kipriyanov SM, Le Gall F (2004) Generation and production of engineered antibodies. Mol Biotechnol 26:39–60PubMedGoogle Scholar
  61. Kohl T, Hitzeroth Q, Stewart D, Varsani A, Govan VA, Christensen ND, Williamson AL, Rybicki EP (2006) Plant-produced Cottontail Rabbit Papillomavirus L1 protein protects against tumor challenge: a proof-of-concept study. Clin Vaccine Immunol 13:845–853PubMedGoogle Scholar
  62. Kohler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497PubMedGoogle Scholar
  63. Kontermann R, Duebel S (eds) (2001) Recombinant antibodies. Springer, BerlinGoogle Scholar
  64. Koprowski H (2005) Vaccines and sera through plant biotechnology. Vaccine 23:1757–1763PubMedGoogle Scholar
  65. Koya V, Moayeri M, Leppla SH, Daniell H (2005) Plant-based vaccine: mice immunized with chloroplast-derived anthrax protective antigen survive anthrax lethal toxin challenge. Infect Immun 73:8266–8274PubMedGoogle Scholar
  66. Kurtzman AL, Govindarajan S, Vahle K, Jones JT, Heinrichs V, Patten PA (2001) Advances in directed protein evolution by recursive genetic recombination: applications to therapeutic proteins. Curr Opin Biotechnol 12:361–370PubMedGoogle Scholar
  67. Lamphear BJ, Jilka JM, Kesl L, Welter M, Howard JA, Streatfield SJ (2004) A corn-based delivery system for animal vaccines: an oral Transmissible Gastroenteritis Virus vaccine boosts lactogenic immunity in swine. Vaccine 22:2420–2424PubMedGoogle Scholar
  68. Lee JY, Yu J, Henderson D, Langridge WH (2004) Plant-synthesized E. coli CFA/I fimbrial protein protects Caco-2 cells from bacterial attachment. Vaccine 23:222–231PubMedGoogle Scholar
  69. Lee RWH, Pool AN, Ziauddin A, Lo RYC, Shewen PE, Strommer JN (2003) Edible vaccine development: stability of Mannheimia haemolytica A1 leukotoxin 50 during post-harvest processing and storage of field-grown transgenic white clover. Mol Breed 11:259–266Google Scholar
  70. Lee RWH, Strommer J, Hodgins D, Shewen PE, Niu Y, Lo RYC (2001) Towards development of an edible vaccine against Bovine Pneumonic Pasteurellosis using transgenic white clover expressing a Mannheimia haemolytica A1 leukotoxin 50 fusion protein. Infect Immun 69:5786–5793PubMedGoogle Scholar
  71. Legocki AB, Miedzinska K, Czaplinska M, Plucieniczak A, Wedrychowicz H (2005) Immunoprotective properties of transgenic plants expressing E2 glycoprotein from CSFV and cysteine protease from Fasciola hepatica. Vaccine 23:1844–1846PubMedGoogle Scholar
  72. Li JT, Fei L, Mou ZR, Wei J, Tang Y, He HY, Wang L, Wu YZ (2006) Immunogenicity of a plant-derived edible Rotavirus subunit vaccine transformed over fifty generations. Virology 356:171–178PubMedGoogle Scholar
  73. Liang W, Huang Y, Yang X, Zhou Z, Pan A, Qian B, Huang C, Chen J, Zhang D (2006) Oral immunization of mice with plant-derived fimbrial adhesin FaeG induces systemic and mucosal K88ad enterotoxigenic Escherichia coli-specific immune responses. FEMS Immunol Med Microbiol 46:393–399PubMedGoogle Scholar
  74. Low NM, Holliger PH, Winter G (1996) Mimicking somatic hypermutation: affinity maturation of antibodies displayed on bacteriophage using a bacterial mutator strain. J Mol Biol 260:359–368PubMedGoogle Scholar
  75. Ma JK, Chikwamba R, Sparrow P, Fischer R, Mahoney R, Twyman RM (2005a) Plant-derived pharmaceuticals – the road forward. Trends Plant Sci 10:580–585PubMedGoogle Scholar
  76. Ma JK, Drake PM, Christou P (2003) The production of recombinant pharmaceutical proteins in plants. Nat Rev Genet 4:794–805PubMedGoogle Scholar
  77. Ma JKC, Barros E, Bock R, Christou P, Dale PJ, Dix PJ, Fischer R, Irwin J, Mahoney R, Pezzotti M, Schillberg S, Sparrow P, Stoger E, Twyman RM (2005b) Molecular farming for new drugs and vaccines – current perspectives on the production of pharmaceuticals in transgenic plants. EMBO Rep 6:593–599PubMedGoogle Scholar
  78. Makvandi-Nejad S, McLean MD, Hirama T, Almquist KC, Mackenzie CR, Hall JC (2005) Transgenic tobacco plants expressing a dimeric single chain variable fragment (scfv) antibody against Salmonella enterica serotype Paratyphi B. Transgenic Res 14:785–792PubMedGoogle Scholar
  79. Maliga P (2003) Progress towards commercialization of plastid transformation technology. Trends Biotechnol 21:20–28PubMedGoogle Scholar
  80. Maliga P (2002) Engineering the plastid genome of higher plants. Curr Opin Plant Biol 5:164–172PubMedGoogle Scholar
  81. Marconi G, Albertini E, Barone P, De Marchis F, Lico C, Marusic C, Rutili D, Veronesi F, Porceddu A (2006) In planta production of two peptides of the Classical Swine Fever Virus (CSFV) E2 glycoprotein fused to the coat protein of Potato Virus X. BMC Biotechnol 6:29PubMedGoogle Scholar
  82. Martin-Alonso JM, Castanon S, Alonso P, Parra F, Ordas R (2003) Oral immunization using tuber extracts from transgenic potato plants expressing Rabbit Hemorrhagic Disease Virus capsid protein. Transgenic Res 12:127–130PubMedGoogle Scholar
  83. Mason HS, Lam DMK, Arntzen CJ (1992) Expression of hepatitis B surface antigen in transgenic plants. Proc Natl Acad Sci USA 89:11745–11749PubMedGoogle Scholar
  84. Molina A, Hervas-Stubbs S, Daniell H, Mingo-Castel AM, Veramendi J (2004) High-yield expression of a viral peptide animal vaccine in transgenic tobacco chloroplasts. Plant Biotechnol J 2:141–153PubMedGoogle Scholar
  85. Molina A, Veramendi J, Hervas-Stubbs S (2005) Induction of neutralizing antibodies by a tobacco chloroplast-derived vaccine based on a B cell epitope from Canine Parvovirus. Virology 342:266–275PubMedGoogle Scholar
  86. Monger W, Alamillo JM, Sola I, Perrin Y, Bestagno M, Burrone OR, Sabella P, Plana-Duran J, Enjuanes L, Garcia JA, Lomonossoff GP (2006) An antibody derivative expressed from viral vectors passively immunizes pigs against Transmissible Gastroenteritis Virus infection when supplied orally in crude plant extracts. Plant Biotechnol J 4:623–631PubMedGoogle Scholar
  87. Natilla A, Hammond RW, Nemchinov LG (2006) Epitope presentation system based on Cucumber Mosaic Virus coat protein expressed from a Potato Virus X-based vector. Arch Virol 151:1373–1386PubMedGoogle Scholar
  88. Nemchinov LG, Paape MJ, Sohn EJ, Bannerman DD, Zarlenga DS, Hammond RW (2006) Bovine CD14 receptor produced in plants reduces severity of intramammary bacterial infection. FASEB J 20:1345–1351PubMedGoogle Scholar
  89. Pavlou AK, Belsey MJ (2005) The therapeutic antibodies market to 2008. Eur J Pharm Biopharm 59:389–396PubMedGoogle Scholar
  90. Pérez Filgueira DM, Mozgovoj M, Wigdorovitz A, Santos MJD, Parreno V, Trono K, Fernandez FM, Carrillo C, Babiuk LA, Morris TJ, Borca MV (2004) Passive protection to Bovine Rotavirus (BRV) infection induced by a BRV VP8* produced in plants using a TMV-based vector. Arch Virol 149:2337–2348PubMedGoogle Scholar
  91. Pérez Filgueira DM, Zamorano PI, Dominguez MG, Taboga O, Zajac MPD, Puntel M, Romera SA, Morris TJ, Borca MV, Sadir AM (2003) Bovine Herpes Virus gD protein produced in plants using a recombinant Tobacco Mosaic Virus (TMV) vector possesses authentic antigenicity. Vaccine 21:4201–4209PubMedGoogle Scholar
  92. Piller KJ, Clemente TE, Jun SM, Petty CC, Sato S, Pascual DW, Bost KL (2005) Expression and immunogenicity of an Escherichia coli K99 fimbriae subunit antigen in soybean. Planta 222:6–18PubMedGoogle Scholar
  93. Prasad V, Satyavathi VV, Valli SKM, Khandelwal A, Shaila MS, Sita GL (2004) Expression of biologically active hemagglutinin-neuraminidase protein of Peste des Petits Ruminants Virus in transgenic pigeonpea [Cajanus cajan (L) Millsp]. Plant Sci 166:199–205Google Scholar
  94. Rigano MM, Alvarez ML, Pinkhasov J, Jin Y, Sala F, Arntzen CJ and Walmsley AM (2004) Production of a fusion protein consisting of the enterotoxigenic Escherichia coli heat-labile toxin B subunit and a tuberculosis antigen in Arabidopsis thaliana. Plant Cell Rep 22:502–508PubMedGoogle Scholar
  95. Saldana S, Guadarrama FE, Flores TDO, Arias N, Lopez S, Arias C, Ruiz-Medrano R, Mason H, Mor T, Richter L, Arntzen CJ, Lim MAG (2006) Production of Rotavirus-like particles in tomato (Lycopersicon esculentum L.) fruit by expression of capsid proteins VP2 and VP6 and immunological studies. Viral Immunol 19:42–53PubMedGoogle Scholar
  96. Satyavathi VV, Prasad V, Khandelwal A, Shaila MS, Sita GL (2003) Expression of hemagglutinin protein of Rinderpest Virus in transgenic pigeon pea [Cajanus cajan (L.) Millsp.] plants. Plant Cell Rep 21:651–658PubMedGoogle Scholar
  97. Scheller J, Henggeler D, Viviani A, Conrad U (2004) Purification of spider silk-elastin from transgenic plants and application for human chondrocyte proliferation. Transgenic Res 13:51–57PubMedGoogle Scholar
  98. Scheller J, Leps M, Conrad U (2006) Forcing single chain variable fragment production in tobacco seeds by fusion to elastin-like polypeptides. Plant Biotechnol J 4:243–249PubMedGoogle Scholar
  99. Scott CT (2005) The problem with potency. Nat Biotechnol 23:1037–1039PubMedGoogle Scholar
  100. Shams H (2005) Recent developments in veterinary vaccinology. Vet J 170:289–299PubMedGoogle Scholar
  101. Stoger E, Ma JKC, Fischer R, Christou P (2005a) Sowing the seeds of success: pharmaceutical proteins from plants. Curr Opin Biotechnol 16:167–173PubMedGoogle Scholar
  102. Stoger E, Sack M, Nicholson L, Fischer R, Christou P (2005b) Recent progress in plantibody technology. Curr Pharm Des 11:2439–2457PubMedGoogle Scholar
  103. Streatfield SJ (2005a) Delivery of plant-derived vaccines. Expert Opin Drug Deliv 2:719–728PubMedGoogle Scholar
  104. Streatfield SJ (2005b) Plant-based vaccines for animal health. Rev Sci Tech Off Int Epiz 24:189–199Google Scholar
  105. Streatfield SJ, Howard JA (2003) Plant-based vaccines. Int J Parasitol 33:479–493PubMedGoogle Scholar
  106. Sussman HE (2003) Spinach makes a safer anthrax vaccine. Drug Discov Today 8:428–430PubMedGoogle Scholar
  107. Usha R, Rohll JB, Spall VE, Shanks M, Maule AJ, Johnson JE, Lomonossoff GP (1993) Expression of an animal virus antigenic site on the surface of a plant-virus particle. Virology 197:366–374PubMedGoogle Scholar
  108. Vermij P, Waltz E (2006) USDA approves the first plant-based vaccine. Nature 24:233–234Google Scholar
  109. Walmsley AM, Alvarez ML, Jin Y, Kirk DD, Lee SM, Pinkhasov J, Rigano MM, Arntzen CJ, Mason HS (2003) Expression of the B subunit of Escherichia coli heat-labile enterotoxin as a fusion protein in transgenic tomato. Plant Cell Rep 21:1020–1026PubMedGoogle Scholar
  110. Warzecha H, Mason HS (2003) Benefits and risks of antibody and vaccine production in transgenic plants. J Plant Physiol 160:755–764PubMedGoogle Scholar
  111. Watson J, Koya V, Leppla SH, Daniell H (2004) Expression of Bacillus anthracis protective antigen in transgenic chloroplasts of tobacco, a non-food/feed crop. Vaccine 22:4374–4384PubMedGoogle Scholar
  112. Wieland WH, Lammers A, Schots A, Orzaez DV (2006) Plant expression of chicken secretory antibodies derived from combinatorial libraries. J Biotechnol 122:382–391PubMedGoogle Scholar
  113. Wigdorovitz A, Mozgovoj M, Santos MJD, Parreno V, Gomez C, Perez-Filgueira DM, Trono KG, Rios RD, Franzone PM, Fernandez F, Carillo C, Babiuk LA, Escribano JM, Borca MV (2004) Protective lactogenic immunity conferred by an edible peptide vaccine to Bovine Rotavirus produced in transgenic plants. J Gen Virol 85:1825–1832PubMedGoogle Scholar
  114. Winter G, Griffiths AD, Hawkins RE, Hoogenboom HR (1994) Making antibodies by phage display technology. Annu Rev Immunol 12:433–455PubMedGoogle Scholar
  115. Woolhouse MEJ, Gowtage-Sequeria S (2005) Host range and emerging and reemerging pathogens. Emerg Infect Dis 11:1842–1847PubMedGoogle Scholar
  116. Wu H, Singh NK, Locy RD, Scissum-Gunn K, Giambrone JJ (2004b) Immunization of chickens with VP2 protein of Infectious Bursal Disease Virus expressed in Arabidopsis thaliana. Avian Dis 48:663–668PubMedGoogle Scholar
  117. Wu H, Singh NK, Locy RD, Scissum-Gunn K, Giambrone JJ (2004a) Expression of immunogenic VP2 protein of Infectious Bursal Disease Virus in Arabidopsis thaliana. Biotechnol Lett 26:787–792PubMedGoogle Scholar
  118. Wu YZ, Li JT, Mou ZR, Fei L, Ni B, Geng M, Jia ZC, Zhou W, Zou LY, Tang Y (2003) Oral immunization with Rotavirus VP7 expressed in transgenic potatoes induced high titers of mucosal neutralizing IgA. Virology 313:337–342PubMedGoogle Scholar
  119. Yu J, Langridge W (2003) Expression of Rotavirus capsid protein VP6 in transgenic potato and its oral immunogenicity in mice. Transgenic Res 12:163–169PubMedGoogle Scholar
  120. Zelada AM, Calarnante G, Santangelo MD, Bigi F, Verna F, Mentaberry A, Cataldi A (2006) Expression of tuberculosis antigen ESAT-6 in Nicotiana tabacum using a Potato Virus X-based vector. Tuberculosis 86:263–267PubMedGoogle Scholar
  121. Zhao Y, Hammond RW (2005) Development of a candidate vaccine for Newcastle Disease Virus by epitope display in the Cucumber Mosaic Virus capsid protein. Biotechnol Lett 27:375–382PubMedGoogle Scholar
  122. Zhou JY, Cheng LQ, Zheng XJ, Wu JX, Shang SB, Wang JY, Chen JG (2004) Generation of the transgenic potato expressing full-length spike protein of Infectious Bronchitis Virus. J Biotechnol 111:121–130PubMedGoogle Scholar
  123. Zhou JY, Wu JX, Cheng LQ, Zheng XJ, Gong H, Shang SB, Zhou EM (2003) Expression of immunogenic S1 glycoprotein of Infectious Bronchitis Virus in transgenic potatoes. J Virol 77:9090–9093PubMedGoogle Scholar
  124. Ziauddin A, Lee RWH, Lo R, Shewen P, Strommer J (2004) Transformation of alfalfa with a bacterial fusion gene, Mannheimia haemolytica A1 leukotoxin50-gfp: response with Agrobacterium tumefaciens strains LBA4404 and C58. Plant Cell Tissue Organ Cult 79:271–278Google Scholar

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© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  • Doreen Manuela Floss
    • 1
  • Dieter Falkenburg
    • 2
  • Udo Conrad
    • 1
  1. 1.Leibniz Institute of Plant Genetics and Crop Plant Research (IPK)GaterslebenGermany
  2. 2.Novoplant GmbHGaterslebenGermany

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