History and Promise of Plant-Made Vaccines for Animals

  • Ed RybickiEmail author


Plant-made vaccines are now a well-established and well-tested concept in veterinary medicine—yet the only product so far licenced was never produced commercially. This is puzzling, given the breadth of exploration of plant-made animal vaccines, and their immunogenicity and efficacy, over more than twenty years of research. The range of candidate vaccines that have been tested in laboratory animal models includes vaccines for E. coli, Salmonella, Yersinia pestis, foot and mouth disease virus, rabbit haemorrhagic disease virus, rabbit and canine and bovine papillomaviruses, mink enteritis and porcine circovirus, and lately also bluetongue virus, among many others. There are many proofs of efficacy of such vaccines, and regulatory pathways appear to have been explored for their licencing. This review will briefly explore the history of plant-made vaccines for use in animals, and will discuss the unique advantages of plant-made vaccines for use in a veterinary medicine setting in detail, with a proposal of their relevance within the “One Health” paradigm.


Plant-made vaccines Therapeutic vaccine One health Transient expression Agrobacterium tumefaciens Nicotiana benthamiana Regulatory cGMP FDA EMEA 


  1. Alvarez ML, Topal E, Martin F, Cardineau GA (2010) Higher accumulation of F1-V fusion recombinant protein in plants after induction of protein body formation. Plant Mol Biol 72:75–89PubMedCrossRefGoogle Scholar
  2. APHIS (2008) Noncompliance historyGoogle Scholar
  3. 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 119:1–14PubMedPubMedCentralCrossRefGoogle Scholar
  4. Athmaram TN, Bali G, Devaiah KM (2006) Integration and expression of Bluetongue VP2 gene in somatic embryos of peanut through particle bombardment method. Vaccine 24:2994–3000PubMedCrossRefGoogle Scholar
  5. Atkinson R, Burt F, Rybicki EP, Meyers AE (2016) Plant-produced Crimean-Congo haemorrhagic fever virus nucleoprotein for use in indirect ELISA. J Virol Methods 236:170–177PubMedCrossRefGoogle Scholar
  6. Aziz MA, Singh S, Anand Kumar P, Bhatnagar R (2002) Expression of protective antigen in transgenic plants: a step towards edible vaccine against anthrax. Biochem Biophys Res Commun 299:345–351PubMedCrossRefGoogle Scholar
  7. 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 19:1501–1503PubMedCrossRefGoogle Scholar
  8. Bethencourt V (2009) Virus stalls Genzyme plant. Nat Biotechnol 27:681CrossRefGoogle Scholar
  9. Biemelt S, Sonnewald U, Galmbacher P, Willmitzer L, Muller M (2003) Production of human papillomavirus type 16 virus-like particles in transgenic plants. J Virol 77:9211–9220PubMedPubMedCentralCrossRefGoogle Scholar
  10. Bonne N, Shearer P, Sharp M, Clark P, Raidal S (2009) Assessment of recombinant beak and feather disease virus capsid protein as a vaccine for psittacine beak and feather disease. J Gen Virol 90:640–647PubMedCrossRefGoogle Scholar
  11. Breitburd F, Kirnbauer R, Hubbert NL, Nonnenmacher B, Trin-Dinh-Desmarquet C, Orth G, Schiller JT, Lowy DR (1995) Immunization with viruslike particles from cottontail rabbit papillomavirus (CRPV) can protect against experimental CRPV infection. J Virol 69:3959–3963PubMedPubMedCentralGoogle Scholar
  12. Breitburd F, Salmon J, Orth G (1997) The rabbit viral skin papillomas and carcinomas: a model for the immunogenetics of HPV-associated carcinogenesis. Clin Dermatol 15:237–247PubMedCrossRefGoogle Scholar
  13. Buyel JF, Fischer R (2014) Generic chromatography-based purification strategies accelerate the development of downstream processes for biopharmaceutical proteins produced in plants. Biotechnol J 9:566–577PubMedCrossRefGoogle Scholar
  14. Buyel JF, Hubbuch J, Fischer R (2016) Comparison of tobacco host cell protein removal methods by blanching intact plants or by heat treatment of extracts. J Visualized Exp: JoVEGoogle Scholar
  15. Carrillo C, Wigdorovitz A, Oliveros JC, Zamorano PI, Sadir AM, 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 72:1688–1690PubMedPubMedCentralGoogle Scholar
  16. Castanon S, Marin MS, Martin-Alonso JM, Boga JA, Casais R, Humara JM, Ordas RJ, Parra F (1999) Immunization with potato plants expressing VP60 protein protects against rabbit hemorrhagic disease virus. J Virol 73:4452–4455PubMedPubMedCentralGoogle Scholar
  17. Castilho A, Strasser R, Stadlmann J, Grass J, Jez J, Gattinger P, Kunert R, Quendler H, Pabst M, Leonard R, Altmann F, Steinkellner H (2010) In planta protein sialylation through overexpression of the respective mammalian pathway. J Biol Chem 285:15923–15930PubMedPubMedCentralCrossRefGoogle Scholar
  18. Castilho A, Steinkellner H (2016) Transient Expression of Mammalian Genes in N. benthamiana to Modulate N-Glycosylation. Methods Mol Biol 1385:99–113PubMedCrossRefGoogle Scholar
  19. Chichester JA, Musiychuk K, de la Rosa P, Horsey A, Stevenson N, Ugulava N, Rabindran S, Palmer GA, Mett V, Yusibov V (2007) Immunogenicity of a subunit vaccine against Bacillus anthracis. Vaccine 25:3111–3114PubMedCrossRefGoogle Scholar
  20. Chichester JA, Manceva SD, Rhee A, Coffin MV, Musiychuk K, Mett V, Shamloul M, Norikane J, Streatfield SJ, Yusibov V (2013) A plant-produced protective antigen vaccine confers protection in rabbits against a lethal aerosolized challenge with Bacillus anthracis Ames spores. Human Vaccines Immunotherapeutics 9:544–552PubMedPubMedCentralCrossRefGoogle Scholar
  21. Chien YJ (2013) How did international agencies perceive the avian influenza problem? The adoption and manufacture of the ‘One World, One Health’ framework. Sociol Health Illn 35:213–226PubMedCrossRefGoogle Scholar
  22. Conley AJ, Joensuu JJ, Jevnikar AM, Menassa R, Brandle JE (2009) Optimization of elastin-like polypeptide fusions for expression and purification of recombinant proteins in plants. Biotechnol Bioeng 103:562–573PubMedCrossRefGoogle Scholar
  23. Conley AJ, Joensuu JJ, Richman A, Menassa R (2011) Protein body-inducing fusions for high-level production and purification of recombinant proteins in plants. Plant Biotechnol J 9:419–433PubMedCrossRefGoogle Scholar
  24. D’Aoust MA, Couture MM, Charland N, Trepanier S, Landry N, Ors F, Vezina LP (2010) The production of hemagglutinin-based virus-like particles in plants: a rapid, efficient and safe response to pandemic influenza. Plant Biotechnol J 8:607–619CrossRefPubMedGoogle Scholar
  25. Dalsgaard K, Uttenthal A, Jones TD, Xu F, Merryweather A, Hamilton WD, Langeveld JP, Boshuizen RS, Kamstrup S, Lomonossoff GP, Porta C, 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
  26. DARPA (2012) DARPA makes 10 million strides in the race to contain a hypothetical pandemic. US Defense Advanced Research Projects AgencyGoogle Scholar
  27. Dus Santos MJ, Wigdorovitz A, Trono K, Rios RD, Franzone PM, Gil F, Moreno J, Carrillo C, Escribano JM, Borca MV (2002) A novel methodology to develop a foot and mouth disease virus (FMDV) peptide-based vaccine in transgenic plants. Vaccine 20:1141–1147PubMedCrossRefGoogle Scholar
  28. Duvenage L, Hitzeroth II, Meyers AE, Rybicki EP (2013) Expression in tobacco and purification of beak and feather disease virus capsid protein fused to elastin-like polypeptides. J Virol Methods 191:55–62PubMedCrossRefGoogle Scholar
  29. Dwyer DE, Kirkland PD (2011) Influenza: one health in action. N S W Public Health Bull 22:123–126PubMedCrossRefGoogle Scholar
  30. Fischer R, Schillberg S, Hellwig S, Twyman RM, Drossard J (2012) GMP issues for recombinant plant-derived pharmaceutical proteins. Biotechnol Adv 30:434–439PubMedCrossRefGoogle Scholar
  31. Ghiasi SM, Salmanian AH, Chinikar S, Zakeri S (2011) Mice orally immunized with a transgenic plant expressing the glycoprotein of Crimean-Congo hemorrhagic fever virus. Clin Vaccine Immunol: CVI 18:2031–2037PubMedCrossRefGoogle Scholar
  32. 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 4:135–143PubMedCrossRefGoogle Scholar
  33. Gleba YY, Tuse D, Giritch A (2014) Plant viral vectors for delivery by Agrobacterium. Curr Top Microbiol Immunol 375:155–192PubMedGoogle Scholar
  34. Gomez N, Wigdorovitz A, Castanon S, Gil F, Ordas R, Borca MV, Escribano JM (2000) Oral immunogenicity of the plant derived spike protein from swine-transmissible gastroenteritis coronavirus. Arch Virol 145:1725–1732PubMedCrossRefGoogle Scholar
  35. Goulet C, Khalf M, Sainsbury F, D’Aoust MA, Michaud D (2012) A protease activity-depleted environment for heterologous proteins migrating towards the leaf cell apoplast. Plant Biotechnol J 10:83–94PubMedCrossRefGoogle Scholar
  36. Hanafi LA, Bolduc M, Gagne ME, Dufour F, Langelier Y, Boulassel MR, Routy JP, Leclerc D, Lapointe R (2010) Two distinct chimeric potexviruses share antigenic cross-presentation properties of MHC class I epitopes. Vaccine 28:5617–5626PubMedCrossRefGoogle Scholar
  37. Haq TA, Mason HS, Clements JD, Arntzen CJ (1995) Oral immunization with a recombinant bacterial antigen produced in transgenic plants. Science 268:714–716PubMedPubMedCentralCrossRefGoogle Scholar
  38. Heath L, Williamson AL, Rybicki EP (2006) The capsid protein of beak and feather disease virus binds to the viral DNA and is responsible for transporting the replication-associated protein into the nucleus. J Virol 80:7219–7225PubMedPubMedCentralCrossRefGoogle Scholar
  39. Hellwig S, Drossard J, Twyman RM, Fischer R (2004) Plant cell cultures for the production of recombinant proteins. Nat Biotechnol 22:1415–1422PubMedCrossRefGoogle Scholar
  40. Herzog RW, Nichols TC, Su J, Zhang B, Sherman A, Merricks EP, Raymer R, Perrin GQ, Häger M, Winberg B, Daniell H (2017) Oral tolerance induction in hemophilia B dogs fed with transplastomic lettuce. Mol Ther 25:512–522PubMedPubMedCentralCrossRefGoogle Scholar
  41. Holtz BR, Berquist BR, Bennett LD, Kommineni VJ, Munigunti RK, White EL, Wilkerson DC, Wong KY, Ly LH, Marcel S (2015) Commercial-scale biotherapeutics manufacturing facility for plant-made pharmaceuticals. Plant Biotechnol J 13:1180–1190PubMedCrossRefGoogle Scholar
  42. 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 18:668–677PubMedCrossRefGoogle Scholar
  43. Huang Z, Chen Q, Hjelm B, Arntzen C, Mason H (2009) A DNA replicon system for rapid high-level production of virus-like particles in plants. Biotechnol Bioeng 103:706–714PubMedPubMedCentralCrossRefGoogle Scholar
  44. Hull AK, Criscuolo CJ, Mett V, Groen H, Steeman W, Westra H, Chapman G, Legutki B, Baillie L, Yusibov V (2005) Human-derived, plant-produced monoclonal antibody for the treatment of anthrax. Vaccine 23:2082–2086PubMedCrossRefGoogle Scholar
  45. Jilka J (2002) An oral vaccine in maize protects against transmissible gastroenteritis virus in swine. In: Erickson L, Yu W-J, Brandle J, Rymerson R (eds) Molecular farming of plants and animals for human and veterinary medicine. Springer, Netherlands, pp 223–236CrossRefGoogle Scholar
  46. Juarez P, Virdi V, Depicker A, Orzaez D (2016) Biomanufacturing of protective antibodies and other therapeutics in edible plant tissues for oral applications. Plant Biotechnol J 14:1791–1799PubMedPubMedCentralCrossRefGoogle Scholar
  47. Kahn RE, Ma W, Richt JA (2014) Swine and influenza: a challenge to one health research. Curr Top Microbiol Immunol 385:205–218PubMedGoogle Scholar
  48. Kashima K, Yuki Y, Mejima M, Kurokawa S, Suzuki Y, Minakawa S, Takeyama N, Fukuyama Y, Azegami T, Tanimoto T, Kuroda M, Tamura M, Gomi Y, Kiyono H (2016) Good manufacturing practices production of a purification-free oral cholera vaccine expressed in transgenic rice plants. Plant Cell Rep 35:667–679PubMedCrossRefGoogle Scholar
  49. 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 323:284–291PubMedCrossRefGoogle Scholar
  50. Kirchhoff J, Raven N, Boes A, Roberts JL, Russell S, Treffenfeldt W, Fischer R, Schinkel H, Schiermeyer A, Schillberg S (2012) Monoclonal tobacco cell lines with enhanced recombinant protein yields can be generated from heterogeneous cell suspension cultures by flow sorting. Plant Biotechnol J 10:936–944PubMedCrossRefGoogle Scholar
  51. Klimyuk V, Pogue G, Herz S, Butler J, Haydon H (2014) Production of recombinant antigens and antibodies in Nicotiana benthamiana using ‘magnifection’ technology: GMP-compliant facilities for small- and large-scale manufacturing. Curr Top Microbiol Immunol 375:127–154PubMedGoogle Scholar
  52. Kohl T, Hitzeroth II, 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 13:845–853PubMedPubMedCentralCrossRefGoogle Scholar
  53. Kortekaas J (2014) One Health approach to Rift Valley fever vaccine development. Antiviral Res 106:24–32PubMedCrossRefGoogle Scholar
  54. 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 73:8266–8274PubMedPubMedCentralCrossRefGoogle Scholar
  55. Lamphear BJ, Streatfield SJ, Jilka JM, Brooks CA, Barker DK, Turner DD, Delaney DE, Garcia M, Wiggins B, Woodard SL, Hood EE, Tizard IR, Lawhorn B, Howard JA (2002) Delivery of subunit vaccines in maize seed. J Control Release 85:169–180PubMedCrossRefGoogle Scholar
  56. Landford J, Nunn M (2012) Good governance in ‘one health’ approaches. Rev Sci Tech 31:561–575PubMedCrossRefGoogle Scholar
  57. LeafBio (2016) LeafBio announces conclusion of ZMapp™ clinical trialGoogle Scholar
  58. Lebel ME, Chartrand K, Leclerc D, Lamarre A (2015) Plant viruses as nanoparticle-based vaccines and adjuvants. Vaccines (Basel) 3:620–637CrossRefGoogle Scholar
  59. Leclerc D, Rivest M, Babin C, Lopez-Macias C, Savard P (2013) A novel M2e based flu vaccine formulation for dogs. PLoS ONE 8:e77084PubMedPubMedCentralCrossRefGoogle Scholar
  60. Leclerc D (2014) Plant viral epitope display systems for vaccine development. Curr Top Microbiol Immunol 375:47–59PubMedGoogle Scholar
  61. Lico C, Benvenuto E, Baschieri S (2015) The two-faced potato virus X: from plant pathogen to smart nanoparticle. Front Plant Sci 6:1009PubMedPubMedCentralCrossRefGoogle Scholar
  62. Ling HY, Edwards AM, Gantier MP, Deboer KD, Neale AD, Hamill JD, Walmsley AM (2012) An interspecific Nicotiana hybrid as a useful and cost-effective platform for production of animal vaccines. PLoS ONE 7:e35688PubMedPubMedCentralCrossRefGoogle Scholar
  63. Love AJ, Chapman SN, Matic S, Noris E, Lomonossoff GP, Taliansky M (2012) In planta production of a candidate vaccine against bovine papillomavirus type 1. PlantaPubMedCrossRefGoogle Scholar
  64. Loza-Rubio E, Rojas E, Gomez L, Olivera MT, Gomez-Lim MA (2008) Development of an edible rabies vaccine in maize using the Vnukovo strain. Dev Biol 131:477–482Google Scholar
  65. Loza-Rubio E, Rojas-Anaya E, Lopez J, Olivera-Flores MT, Gomez-Lim M, Tapia-Perez G (2012) Induction of a protective immune response to rabies virus in sheep after oral immunization with transgenic maize, expressing the rabies virus glycoprotein. Vaccine 30:5551–5556PubMedPubMedCentralCrossRefGoogle Scholar
  66. Ludwig S, Zell R, Schwemmle M, Herold S (2014) Influenza, a One Health paradigm–novel therapeutic strategies to fight a zoonotic pathogen with pandemic potential. Int J Med Microbiol 304:894–901PubMedCrossRefGoogle Scholar
  67. Ma JK, Drossard J, Lewis D, Altmann F, Boyle J, Christou P, Cole T, Dale P, van Dolleweerd CJ, Isitt V, Katinger D, Lobedan M, Mertens H, Paul MJ, Rademacher T, Sack M, Hundleby PA, Stiegler G, Stoger E, Twyman RM, Vcelar B, Fischer R (2015) Regulatory approval and a first-in-human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants. Plant Biotechnol J 13:1106–1120PubMedCrossRefGoogle Scholar
  68. MacDonald J, Doshi K, Dussault M, Hall JC, Holbrook L, Jones G, Kaldis A, Klima CL, Macdonald P, McAllister T, McLean MD, Potter A, Richman A, Shearer H, Yarosh O, Yoo HS, Topp E, Menassa R (2015) Bringing plant-based veterinary vaccines to market: managing regulatory and commercial hurdles. Biotechnol Adv 33:1572–1581PubMedCrossRefGoogle Scholar
  69. Mackenzie JS, Field HE, Guyatt KJ (2003) Managing emerging diseases borne by fruit bats (flying foxes), with particular reference to henipaviruses and Australian bat lyssavirus. J Appl Microbiol 94(Suppl):59S–69SPubMedCrossRefGoogle Scholar
  70. Maclean J, Koekemoer M, Olivier AJ, Stewart D, Hitzeroth II, Rademacher T, Fischer R, Williamson AL, Rybicki EP (2007) Optimization of human papillomavirus type 16 (HPV-16) L1 expression in plants: comparison of the suitability of different HPV-16 L1 gene variants and different cell-compartment localization. J Gen Virol 88:1460–1469PubMedCrossRefGoogle Scholar
  71. Mamedov T, Yusibov V (2013) In vivo deglycosylation of recombinant proteins in plants by co-expression with bacterial PNGase F. Bioengineered 4:338–342PubMedPubMedCentralCrossRefGoogle Scholar
  72. Mandal MK, Fischer R, Schillberg S, Schiermeyer A (2014) Inhibition of protease activity by antisense RNA improves recombinant protein production in Nicotiana tabacum cv. Bright Yellow 2 (BY-2) suspension cells. Biotechnol J 9:1065–1073PubMedCrossRefGoogle Scholar
  73. Mbewana S, Mortimer E, Pera FF, Hitzeroth II, Rybicki EP (2015) Production of H5N1 influenza virus matrix protein 2 ectodomain protein bodies in tobacco plants and in insect cells as a candidate universal influenza vaccine. Front Bioeng Biotechnol 3:197PubMedPubMedCentralCrossRefGoogle Scholar
  74. Miletic S, Simpson DJ, Szymanski CM, Deyholos MK, Menassa R (2015) A plant-produced bacteriophage tailspike protein for the control of salmonella. Front Plant Sci 6:1221PubMedGoogle Scholar
  75. Monath TP (2013) Vaccines against diseases transmitted from animals to humans: a one health paradigm. Vaccine 31:5321–5338PubMedCrossRefGoogle Scholar
  76. Nemchinov LG, Natilla A (2007) Transient expression of the ectodomain of matrix protein 2 (M2e) of avian influenza A virus in plants. Protein Expr Purif 56:153–159CrossRefPubMedGoogle Scholar
  77. Niedbalski W (2011) Bluetongue vaccines in Europe. Pol J Vet Sci 14:299–304PubMedGoogle Scholar
  78. Palmer KE, Benko A, Doucette SA, Cameron TI, Foster T, Hanley KM, McCormick AA, McCulloch M, Pogue GP, Smith ML, Christensen ND (2006) Protection of rabbits against cutaneous papillomavirus infection using recombinant tobacco mosaic virus containing L2 capsid epitopes. Vaccine 24:5516–5525PubMedCrossRefGoogle Scholar
  79. Pasquevich KA, Ibanez AE, Coria LM, Garcia Samartino C, Estein SM, Zwerdling A, Barrionuevo P, Oliveira FS, Seither C, Warzecha H, Oliveira SC, Giambartolomei GH, Cassataro J (2011) An oral vaccine based on U-Omp19 induces protection against B. abortus mucosal challenge by inducing an adaptive IL-17 immune response in mice. PLoS ONE 6:e16203PubMedPubMedCentralCrossRefGoogle Scholar
  80. Patterson EI, Swarbrick CM, Roman N, Forwood JK, Raidal SR (2013) Differential expression of two isolates of beak and feather disease virus capsid protein in Escherichia coli. J Virol Methods 189:118–124PubMedCrossRefGoogle Scholar
  81. Pearson LD, Roy P (1993) Genetically engineered multi-component virus-like particles as veterinary vaccines. Immunol Cell Biol 71(Pt 5):381–389PubMedCrossRefGoogle Scholar
  82. Perez Filgueira DM, Mozgovoj M, Wigdorovitz A, Dus Santos MJ, 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 149:2337–2348PubMedCrossRefGoogle Scholar
  83. Powdrill TF, Nipp TL, Rinderknecht JL (2010) One health approach to influenza: assessment of critical issues and options. Emerg Infect Dis 16:e1PubMedCrossRefGoogle Scholar
  84. Protalix (2017) Orally delivered proteinsGoogle Scholar
  85. Purse BV, Brown HE, Harrup L, Mertens PP, Rogers DJ (2008) Invasion of bluetongue and other orbivirus infections into Europe: the role of biological and climatic processes. Rev Sci Tech 27:427–442PubMedCrossRefGoogle Scholar
  86. Rademacher T (2014) Method for the generation and cultivation of a plant cell pack. Google PatentsGoogle Scholar
  87. Regnard GL, Halley-Stott RP, Tanzer FL, Hitzeroth II, Rybicki EP (2010) High level protein expression in plants through the use of a novel autonomously replicating geminivirus shuttle vector. Plant Biotechnol J 8:38–46PubMedCrossRefGoogle Scholar
  88. Risso GS, Carabajal MV, Bruno LA, Ibanez AE, Coria LM, Pasquevich KA, Lee SJ, McSorley SJ, Briones G, Cassataro J (2017) U-Omp19 from brucella abortus is a useful adjuvant for vaccine formulations against salmonella infection in mice. Front Immunol 8:171PubMedPubMedCentralCrossRefGoogle Scholar
  89. Robert S, Khalf M, Goulet MC, D’Aoust MA, Sainsbury F, Michaud D (2013) Protection of recombinant mammalian antibodies from development-dependent proteolysis in leaves of Nicotiana benthamiana. PLoS ONE 8:e70203PubMedPubMedCentralCrossRefGoogle Scholar
  90. Roy P, Bishop DH, LeBlois H, Erasmus BJ (1994) Long-lasting protection of sheep against bluetongue challenge after vaccination with virus-like particles: evidence for homologous and partial heterologous protection. Vaccine 12:805–811PubMedCrossRefGoogle Scholar
  91. Rybicki EP (2009) Plant-produced vaccines: promise and reality. Drug Discov Today 14:16–24PubMedCrossRefGoogle Scholar
  92. Rybicki EP (2010) Plant-made vaccines for humans and animals. Plant Biotechnol J 8:620–637PubMedCrossRefGoogle Scholar
  93. Rybicki EP (2014) Plant-based vaccines against viruses. Virol J 11:205PubMedPubMedCentralCrossRefGoogle Scholar
  94. Rybicki EP, Martin DP (2014) Virus-derived ssDNA vectors for the expression of foreign proteins in plants. Curr Top Microbiol Immunol 375:19–45PubMedGoogle Scholar
  95. Sainsbury F, Lavoie PO, D’Aoust MA, Vezina LP, Lomonossoff GP (2008) Expression of multiple proteins using full-length and deleted versions of cowpea mosaic virus RNA-2. Plant Biotechnol J 6:82–92PubMedGoogle Scholar
  96. Sainsbury F, Thuenemann EC, Lomonossoff GP (2009) pEAQ: versatile expression vectors for easy and quick transient expression of heterologous proteins in plants. Plant Biotechnol J 7:682–693PubMedPubMedCentralCrossRefGoogle Scholar
  97. Sainsbury F, Jutras PV, Vorster J, Goulet MC, Michaud D (2016) A chimeric affinity tag for efficient expression and chromatographic purification of heterologous proteins from plants. Front Plant Sci 7:141PubMedPubMedCentralCrossRefGoogle Scholar
  98. Sarker S, Ghorashi SA, Swarbrick CM, Khandokar YB, Himiari Z, Forwood JK, Raidal SR (2015) An efficient approach for recombinant expression and purification of the viral capsid protein from beak and feather disease virus (BFDV) in Escherichia coli. J Virol Methods 215–216:1–8PubMedCrossRefGoogle Scholar
  99. 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
  100. Saxena P, Thuenemann EC, Sainsbury F, Lomonossoff GP (2016) Virus-derived vectors for the expression of multiple proteins in plants. Methods Mol Biol 1385:39–54PubMedCrossRefGoogle Scholar
  101. Shamloul M, Trusa J, Mett V, Yusibov V (2014) Optimization and utilization of agrobacterium-mediated transient protein production in nicotiana. J Vis Exp: JoVEGoogle Scholar
  102. Short KR, Richard M, Verhagen JH, van Riel D, Schrauwen EJ, van den Brand JM, Manz B, Bodewes R, Herfst S (2015) One health, multiple challenges: the inter-species transmission of influenza A virus. One Health 1:1–13PubMedPubMedCentralCrossRefGoogle Scholar
  103. Specht EA, Mayfield SP (2014) Algae-based oral recombinant vaccines. Front Microbiol 5:60PubMedPubMedCentralCrossRefGoogle Scholar
  104. Steele JF, Peyret H, Saunders K, Castells-Graells R, Marsian J, Meshcheriakova Y, Lomonossoff GP (2017) Synthetic plant virology for nanobiotechnology and nanomedicine. Wiley Interdiscip Rev Nanomed NanobiotechnolGoogle Scholar
  105. Steinkellner H, Castilho A (2015) N-Glyco-engineering in plants: update on strategies and major achievements. Methods Mol Biol 1321:195–212PubMedCrossRefGoogle Scholar
  106. Stewart ME, Bonne N, Shearer P, Khalesi B, Sharp M, Raidal S (2007) Baculovirus expression of beak and feather disease virus (BFDV) capsid protein capable of self-assembly and haemagglutination. J Virol Methods 141:181–187PubMedCrossRefGoogle Scholar
  107. Strasser R, Stadlmann J, Schahs M, Stiegler G, Quendler H, Mach L, Glossl J, Weterings K, Pabst M, Steinkellner H (2008) Generation of glyco-engineered Nicotiana benthamiana for the production of monoclonal antibodies with a homogeneous human-like N-glycan structure. Plant Biotechnol J 6:392–402PubMedPubMedCentralCrossRefGoogle Scholar
  108. Streatfield SJ, Lane JR, Brooks CA, Barker DK, Poage ML, Mayor JM, Lamphear BJ, Drees CF, Jilka JM, Hood EE, Howard JA (2003) Corn as a production system for human and animal vaccines. Vaccine 21:812–815PubMedCrossRefGoogle Scholar
  109. Tabayashi N, Matsumura T (2014) Forefront study of plant biotechnology for practical use: development of oral drug for animal derived from transgenic strawberry. Soc Biotechnol J Japn 92:537–539Google Scholar
  110. Tackaberry ES, Prior F, Bell M, Tocchi M, Porter S, Mehic J, Ganz PR, Sardana R, Altosaar I, Dudani A (2003) Increased yield of heterologous viral glycoprotein in the seeds of homozygous transgenic tobacco plants cultivated underground. Genome 46:521–526PubMedCrossRefGoogle Scholar
  111. Thuenemann EC, Meyers AE, Verwey J, Rybicki EP, Lomonossoff GP (2013) A method for rapid production of heteromultimeric protein complexes in plants: assembly of protective bluetongue virus-like particles. Plant Biotechnol J 11:839–846PubMedPubMedCentralCrossRefGoogle Scholar
  112. Topp E, Irwin R, McAllister T, Lessard M, Joensuu JJ, Kolotilin I, Conrad U, Stoger E, Mor T, Warzecha H, Hall JC, McLean MD, Cox E, Devriendt B, Potter A, Depicker A, Virdi V, Holbrook L, Doshi K, Dussault M, Friendship R, Yarosh O, Yoo HS, MacDonald J, Menassa R (2016) The case for plant-made veterinary immunotherapeutics. Biotechnol Adv 34:597–604PubMedPubMedCentralCrossRefGoogle Scholar
  113. Torrent M, Llop-Tous I, Ludevid MD (2009) Protein body induction: a new tool to produce and recover recombinant proteins in plants. Methods Mol Biol 483:193–208PubMedCrossRefGoogle Scholar
  114. Twyman RM, Schillberg S, Fischer R (2013) Optimizing the yield of recombinant pharmaceutical proteins in plants. Curr Pharm Des 19:5486–5494PubMedCrossRefGoogle Scholar
  115. Tyulkina LG, Skurat EV, Frolova OY, Komarova TV, Karger EM, Atabekov IG (2011) New viral vector for superproduction of epitopes of vaccine proteins in plants. Acta Naturae 3:73–82PubMedPubMedCentralGoogle Scholar
  116. 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 197:366–374PubMedCrossRefGoogle Scholar
  117. Varsani A, Williamson AL, Rose RC, Jaffer M, Rybicki EP (2003) Expression of Human papillomavirus type 16 major capsid protein in transgenic Nicotiana tabacum cv. Xanthi. Arch Virol 148:1771–1786PubMedCrossRefGoogle Scholar
  118. Vasilev N, Gromping U, Lipperts A, Raven N, Fischer R, Schillberg S (2013) Optimization of BY-2 cell suspension culture medium for the production of a human antibody using a combination of fractional factorial designs and the response surface method. Plant Biotechnol J 11:867–874PubMedCrossRefGoogle Scholar
  119. Virdi V, Coddens A, De Buck S, Millet S, Goddeeris BM, Cox E, De Greve H, Depicker A (2013) Orally fed seeds producing designer IgAs protect weaned piglets against enterotoxigenic Escherichia coli infection. Proc Natl Acad Sci U S A 110:11809–11814PubMedPubMedCentralCrossRefGoogle Scholar
  120. Warzecha H, Mason HS, Lane C, Tryggvesson A, Rybicki E, Williamson AL, Clements JD, Rose RC (2003) Oral immunogenicity of human papillomavirus-like particles expressed in potato. J Virol 77:8702–8711PubMedPubMedCentralCrossRefGoogle Scholar
  121. 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 22:4374–4384PubMedPubMedCentralCrossRefGoogle Scholar
  122. Wigdorovitz A, Carrillo C, Dus Santos MJ, Trono K, Peralta A, Gomez MC, Rios RD, Franzone PM, Sadir AM, Escribano JM, Borca MV (1999a) Induction of a protective antibody response to foot and mouth disease virus in mice following oral or parenteral immunization with alfalfa transgenic plants expressing the viral structural protein VP1. Virology 255:347–353PubMedCrossRefGoogle Scholar
  123. Wigdorovitz A, Perez Filgueira DM, Robertson N, Carrillo C, Sadir AM, Morris TJ, Borca MV (1999b) Protection of mice against challenge with foot and mouth disease virus (FMDV) by immunization with foliar extracts from plants infected with recombinant tobacco mosaic virus expressing the FMDV structural protein VP1. Virology 264:85–91PubMedCrossRefGoogle Scholar
  124. Wigdorovitz A, Mozgovoj M, Santos MJ, Parreno V, Gomez C, Perez-Filgueira DM, Trono KG, Rios RD, Franzone PM, Fernandez F, Carrillo 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 85:1825–1832PubMedCrossRefGoogle Scholar
  125. Wirblich C, Coleman CM, Kurup D, Abraham TS, Bernbaum JG, Jahrling PB, Hensley LE, Johnson RF, Frieman MB, Schnell MJ (2017) One-Health: a safe, efficient, dual-use vaccine for humans and animals against middle east respiratory syndrome coronavirus and rabies virus. J Virol 91Google Scholar
  126. Yang C-D, Liao J-T, Lai C-Y, Jong M-H, Liang C-M, Lin Y-L, Lin N-S, Hsu Y-H, Liang S-M (2007a) Induction of protective immunity in swine by recombinant bamboo mosaic virus expressing foot-and-mouth disease virus epitopes. BMC Biotechnol 7:62PubMedPubMedCentralCrossRefGoogle Scholar
  127. Yang ZQ, Liu QQ, Pan ZM, Yu HX, Jiao XA (2007b) Expression of the fusion glycoprotein of Newcastle disease virus in transgenic rice and its immunogenicity in mice. Vaccine 25:591–598CrossRefPubMedGoogle Scholar
  128. Yu J, Langridge WH (2001) A plant-based multicomponent vaccine protects mice from enteric diseases. Nat Biotechnol 19:548–552PubMedCrossRefGoogle Scholar
  129. Yusibov V, Hooper DC, Spitsin SV, Fleysh N, Kean RB, Mikheeva T, Deka D, Karasev A, Cox S, Randall J, Koprowski H (2002) Expression in plants and immunogenicity of plant virus-based experimental rabies vaccine. Vaccine 20:3155–3164PubMedPubMedCentralCrossRefGoogle Scholar
  130. 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 27:375–382PubMedCrossRefGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Biopharming Research Unit, Department of Molecular and Cell BiologyUniversity of Cape TownCape TownSouth Africa

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