Diseases with Limited Research of Plant-Based Vaccines

  • Ann MeyersEmail author


There are a number of diseases which are important globally in terms of the effect they have on livestock but for which the development of recombinant plant-produced vaccines is preliminary. For many of these diseases such as bovine viral diarrhoea (BVD), bovine rotavirus (BRV), bovine herpes (BoH), transmissible gastroenteritis (TGE) in pigs, infectious bronchitis (IB) in chickens, bluetongue (BT) in sheep, Rift Valley fever (RVF) in sheep and coccidiosis in chickens, commercially available live-attenuated or killed vaccines are available. Although most are effective to varying degrees, there are numerous issues with manufacture and potential reassortment of the vaccine strains. For some diseases such as bovine papillomavirus (BPV) infections and Crimean-Congo haemorrhagic fever (CCHF), there are no commercially available vaccines, and limited studies have been conducted on their development. This chapter discusses some of the research developments in plant-produced vaccine candidates which have potential for further development towards commercialisation.




  1. Abrantes J, van der Loo W, Le Pendu J, Esteves PJ (2012) Rabbit haemorrhagic disease (RHD) and rabbit haemorrhagic disease virus (RHDV): a review. Vet Res 43(1):12–12. Scholar
  2. Aguirreburualde MSP et al (2013) Efficacy of a BVDV subunit vaccine produced in alfalfa transgenic plants. Vet Immunol Immunopathol 151(3–4):315–324. Scholar
  3. Alves DL, Pereira LLF, van Drunen LH (2014) Bovine herpesvirus glycoprotein D: a review of its structural characteristics and applications in vaccinology. Vet Res 45(1):111. Scholar
  4. Bande F, Arshad SS, Hair Bejo M, Moeini H, Omar AR (2015) Progress and challenges toward the development of vaccines against avian infectious bronchitis. J Immunol Res 2015:12. Scholar
  5. Bente DA, Forrester NL, Watts DM, McAuley AJ, Whitehouse CA, Bray M (2013) Crimean-Congo hemorrhagic fever: history, epidemiology, pathogenesis, clinical syndrome and genetic diversity. Antiviral Res 100(1):159–189. Scholar
  6. Bhanuprakash V, Indrani BK, Hosamani M, Balamurugan V, Singh RK (2009) Bluetongue vaccines: the past, present and future. Expert Rev Vaccines 8(2):191–204. Scholar
  7. Borzacchiello G, Roperto F (2008) Bovine papillomaviruses, papillomas and cancer in cattle. Vet Res 39(5):45CrossRefPubMedGoogle Scholar
  8. Bouloy M, Flick R (2009) Reverse genetics technology for Rift Valley fever virus: current and future applications for the development of therapeutics and vaccines. Antiviral Res 84(2):101–118. Scholar
  9. Brock KV, Grooms DL, Givens MD (2008) Reproductive disease and persistent infections bovine viral diarrhea virus. Blackwell, Oxford, pp 145–156Google Scholar
  10. Campo MS (1995) Infection by bovine papillomavirus and prospects for vaccination. Trends Microbiol 3(3):92–97CrossRefPubMedGoogle Scholar
  11. Carpenter S, Mellor PS, Torr SJ (2008) Control techniques for Culicoides biting midges and their application in the U.K. and northwestern Palearctic. Med Vet Entemol 22:175–187CrossRefGoogle Scholar
  12. Castañón S et al (1999) Immunization with potato plants expressing VP60 protein protects against rabbit hemorrhagic disease virus. J Virol 73(5):4452–4455PubMedPubMedCentralGoogle Scholar
  13. Cavanagh D, Davis PJ, Darbyshire JH, Peters RW (1986) Coronavirus IBV: virus retaining spike glycopolypeptide S2 but not S1 is unable to induce virus-neutralizing or haemagglutination-inhibiting antibody, or induce chicken tracheal protection. J Gen Virol 67(7):1435–1442. Scholar
  14. Chen EY, Howley PM, Levinson AD, Seeburg PH (1982) The primary structure and genetic organization of the bovine papillomavirus type 1 genome. Nature 299(5883):529–534CrossRefPubMedGoogle Scholar
  15. Choi KH et al (2004) The structure of the RNA-dependent RNA polymerase from bovine viral diarrhea virus establishes the role of GTP in de novo initiation. Proc Natl Acad Sci USA 101(13):4425–4430. Scholar
  16. Christova I, Kovacheva O, Georgieva G, Ivanova S, Argirov D (2010) Vaccine against Congo-crimean haemorrhagic fever virus—Bulgarian input in fighting the disease. ProblInfectParasitDis 37:7–8Google Scholar
  17. Cosby KC, Yamanouchi K (2006) Immunology of rinderpest—an immunosuppression but a lifelong vaccine protection. In: Barrett T, Pastoret P-P, Taylor W (eds) Rinderpest and Peste des Petits Ruminants. Elsevier, Oxford, UK, pp 196–222CrossRefGoogle Scholar
  18. de Boer SM et al (2010) Rift valley fever virus subunit vaccines confer complete protection against a lethal virus challenge. Vaccine 28:2330–2339CrossRefPubMedGoogle Scholar
  19. Dhama K, Chauhan RS, Mahendran M, Malik SVS (2009) Rotavirus diarrhea in bovines and other domestic animals. Vet Res Commun 33(1):1–23. Scholar
  20. Dong J-L, Liang B-G, Jin Y-S, Zhang W-J, Wang T (2005) Oral immunization with pBsVP6-transgenic alfalfa protects mice against rotavirus infection. Virology 339(2):153–163. Scholar
  21. Elbers ARW, van der Spek AN, van Rijn PA (2009) Epidemiologic characteristics of bluetongue virus serotype 8 laboratory-confirmed outbreaks in The Netherlands in 2007 and a comparison with the situation in 2006. Prev Vet Med 92(1–2):1–8. Scholar
  22. Fernández-Fernández MR, Mouriño M, Rivera J, Rodríguez F, Plana-Durán J, García JA (2001) Protection of rabbits against rabbit hemorrhagic disease virus by immunization with the VP60 protein expressed in plants with a potyvirus-based vector. Virology 280(2):283–291. Scholar
  23. Filgueira DP et al. (2003) Bovine herpes virus gD protein produced in plants using a recombinant tobacco mosaic virus (TMV) vector possesses authentic antigenicity. Vaccine 21
  24. French TJ, Marshall JJ, Roy P (1990) Assembly of double-shelled, virus like particles of bluetongue virus by the simultaneous expression of four structural proteins. J Virol 64(12):5695–5700PubMedPubMedCentralGoogle Scholar
  25. Fulton RW (2008) Vaccines bovine viral diarrhea virus. Blackwell, Oxford, pp 209–222Google Scholar
  26. Gao Y et al (2015) A transgenic ginseng vaccine for bovine viral diarrhea. Virol J 12:73. Scholar
  27. Ghiasi SM et al (2012) Molecular farming, an effective system for the production of immunogenic Crimean-Congo Hemorrhagic fever virus glycoprotein. Prog Biol Sci 2(1):12–29Google Scholar
  28. Gómez N, Carrillo C, Salinas J, Parra F, Borca MV, Escribano JM (1998) Expression of immunogenic glycoprotein S polypeptides from transmissible gastroenteritis coronavirus in transgenic plants. Virology 249(2):352–358. Scholar
  29. Gómez N et al (2000) Oral immunogenicity of the plant derived spike protein from swine-transmissible gastroenteritis coronavirus. Adv Virol 145(8):1725–1732. Scholar
  30. Graham DA (2013) Bovine herpes virus-1 (BoHV-1) in cattle—a review with emphasis on reproductive impacts and the emergence of infection in Ireland and the United Kingdom. Irish Vet J 66(1):15–15. Scholar
  31. Habjan M et al (2009) Efficient production of Rift Valley fever virus-like particles: the antiviral protein MxA can inhibit primary transcription of bunyaviruses. Virology 385(2):400–408. Scholar
  32. Hamad MA, Al-Shammari AM, Odisho SM, Yaseen NY (2016) Molecular and phylogenetic analysis of bovine papillomavirus type 1: first report in Iraqi cattle. Adv Virol 2016:7. Scholar
  33. Hammond RW, Nemchinov LG (2009) Plant production of veterinary vaccines and therapeutics. In: Karasev AV (ed) Plant-produced Microbial Vaccines, vol 332. Springer, Berlin, pp 79–102CrossRefGoogle Scholar
  34. Hoogstraal H (1979) The epidemiology of tick-borne Crimean-Congo hemorrhagic fever in Asia, Europe and Africa. J Med Entomol 15:307–417CrossRefPubMedGoogle Scholar
  35. Ikegami T, Makino S (2009) Rift valley fever vaccines. Vaccine 27(Supplement 4):D69–D72. Scholar
  36. Jackwood MW (2012) Review of infectious bronchitis virus around the world. Avian Dis 56(4):634–641. Scholar
  37. Jenckel M et al (2015) Complete coding genome sequence of putative novel bluetongue virus serotype 27. Genome Announcements 3(2) 10.1128/genomea.00016-15CrossRefPubMedPubMedCentralGoogle Scholar
  38. Johnson MA, Pooley C, Ignjatovic J, Tyack SG (2003) A recombinant fowl adenovirus expressing the S1 gene of infectious bronchitis virus protects against challenge with infectious bronchitis virus. Vaccine 21(21–22):2730–2736. Scholar
  39. Kalbina I et al (2016) Arabidopsis thaliana plants expressing rift valley fever virus antigens: mice exhibit systemic immune responses as the result of oral administration of the transgenic plants. Protein Expr Purif 127:61–67. Scholar
  40. Keshtkar-Jahromi M, Kuhn JH, Christova I, Bradfute SB, Jahrling PB, Bavari S (2011) Crimean-Congo hemorrhagic fever: current and future prospects of vaccines and therapies. Antiviral Res 90(2):85–92. Scholar
  41. Khandelwal A, Lakshmi Sita G, Shaila MS (2003) Oral immunization of cattle with hemagglutinin protein of rinderpest virus expressed in transgenic peanut induces specific immune responses. Vaccine 21(23):3282–3289. Scholar
  42. 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(2):284–291. Scholar
  43. Kirnbauer R, Booy F, Cheng N, Lowy DR, Schiller JT (1992) Papillomavirus L1 major capsid protein self-assembles into virus-like particles that are highly immunogenic. Proc Natl Acad Sci 89(24):12180–12184CrossRefPubMedGoogle Scholar
  44. Labbé M, Charpilienne A, Crawford SE, Estes MK, Cohen J (1991) Expression of rotavirus VP2 produces empty core like particles. J Virol 65(6):2946–2952PubMedPubMedCentralGoogle Scholar
  45. Lamphear BJ et al (2002) Delivery of subunit vaccines in maize seed. J Control Release 85(1–3):169–180. Scholar
  46. 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(19):2420–2424. Scholar
  47. Lanyon SR, Hill FI, Reichel MP, Brownlie J (2014) Bovine viral diarrhoea: pathogenesis and diagnosis. Vet J 199(2):201–209. Scholar
  48. Laude H, Rasschaert D, Delmas B, Godet M, Gelfi J, Charley B (1990) Molecular biology of transmissible gastroenteritis virus. Vet Microbiol 23(1):147–154. Scholar
  49. Lentz EM, Mozgovoj MV, Bellido D, Santos MJD, Wigdorovitz A, Bravo-Almonacid FF (2011) VP8* antigen produced in tobacco transplastomic plants confers protection against bovine rotavirus infection in a suckling mouse model. J Biotechnol 156(2):100–107. Scholar
  50. Liu L, Celma CCP, Roy P (2008) Rift valley fever virus structural proteins: expression, characterization and assembly of recombinant proteins. Virol J 5:82–82. Scholar
  51. 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. Planta 236(4):1305–1313. Scholar
  52. Maan NS et al (2012) Identification and differentiation of the twenty six bluetongue virus serotypes by RT–PCR Amplification of the serotype-specific genome segment 2. PLoS ONE 7(2):e32601. Scholar
  53. Maclachlan N, Drew C, Darpel K, Worwa G (2009) The pathology and pathogenesis of bluetongue. J Comp Pathol 141:1–16CrossRefPubMedGoogle Scholar
  54. Martin SJ (1986) The structure and composition of morbilliviruses: a brief review. Rev Sci Tech Off Int Epiz 5(9):389–393CrossRefGoogle Scholar
  55. Martín-Alonso JM, Castañón S, Alonso P, Parra F, Ordás R (2003) Oral immunization using tuber extracts from transgenic potato plants expressing rabbit hemorrhagic disease virus capsid protein. Transgenic Res 12(1):127–130. Scholar
  56. Matsumura T, Itchoda N, Tsunemitsu H (2002) Production of immunogenic VP6 protein of bovine group A rotavirus in transgenic potato plants. Adv Virol 147(6):1263–1270. Scholar
  57. Mertens PP, Diprose J, Maan S, Singh KP, Attoui H, Samuel AR (2004) Bluetongue virus replication, molecular and structural biology. Vet Ital 40(4):426–37PubMedGoogle Scholar
  58. Munday JS (2014) Bovine and human papillomaviruses. Vet Pathol 51(6):1063–1075. Scholar
  59. Muylkens B, Thiry J, Kirten P, Schynts F, Thiry E (2007) Bovine herpesvirus 1 infection and infectious bovine rhinotracheitis. Vet Res 38(2):181–209CrossRefPubMedGoogle Scholar
  60. Näslund J et al (2009) Vaccination with virus-like particles protects mice from lethal infection of rift valley fever virus. Virology 385(2):409–415. Scholar
  61. Nelson G, Marconi P, Periolo O, La Torre J, Alvarez MA (2012) Immunocompetent truncated E2 glycoprotein of bovine viral diarrhea virus (BVDV) expressed in nicotiana tabacum plants: a candidate antigen for new generation of veterinary vaccines. Vaccine 30(30):4499–4504. Scholar
  62. OIE (2008a) Rinderpest, vol Ch 2.1.15Google Scholar
  63. OIE (2008b) Transmissible gastroenteritis, vol Ch 2.8.11Google Scholar
  64. Papp H et al (2013) Review of group A rotavirus strains reported in swine and cattle. Vet Microbiol 165(3–4):190–199. Scholar
  65. Pecora A, Aguirreburualde MSP, Aguirreburualde A, Leunda MR, Odeon A, Chiavenna S, Bochoeyer D, Spitteler M, Filippi JL, Santos MJD, Levy SM (2012) Safety and efficacy of an E2 glycoprotein subunit vaccine produced in mammalian cells to prevent experimental infection with bovine viral diarrhoea virus in cattle. Vet Res Commun 36(3):157–164.CrossRefPubMedGoogle Scholar
  66. Pepin M, Bouloy M, Bird BH, Kemp A, Paweska J (2010) Rift valley fever virus (Bunyaviridae: Phlebovirus): an update on pathogenesis, molecular epidemiology, vectors, diagnostics and prevention. Vet Res 41(6) Scholar
  67. Plowright W, Ferris RD (1962) Studies with rinderpest virus in tissue culture: the use of attenuated culture virus as a vaccine in cattle. Res Vet Sci 3:172–182Google Scholar
  68. Price KR (2012) Use of live vaccines for coccidiosis control in replacement layer pullets. J Appl Poult Res 21(3):679–692. Scholar
  69. Raj GD, Jones RC (1997) Infectious bronchitis virus: immunopathogenesis of infection in the chicken. Avian Pathol 26(4):677–706. Scholar
  70. Ridpath JF (2013) Immunology of BVDV vaccines. Biologicals 41(1):14–19. Scholar
  71. Roeder P, Mariner J, Kock R (2013) Rinderpest: the veterinary perspective on eradication. Philos Trans R Soc Lond B Biol Sci 368:20120139CrossRefPubMedPubMedCentralGoogle Scholar
  72. Roy P (1992) Bluetongue virus proteins. J Gen Virol 73(Pt 12):3051–64CrossRefPubMedGoogle Scholar
  73. Ruiz V, Mozgovoj MV, Dus Santos MJ, Wigdorovitz A (2015) Plant-produced viral bovine vaccines: what happened during the last 10 years? Plant Biotechnol J 13(8):1071–1077. Scholar
  74. Saif LJ, Fernandez FM (1996) Group A rotavirus veterinary vaccines. J Infect Dis 174(Supplement_1):S98-S106 Scholar
  75. Saif LJ, van Cott JL, Brim TA (1994) Immunity to transmissible gastroenteritis virus and porcine respiratory coronavirus infections in swine. Vet Immunol Immunopathol 43(1):89–97. Scholar
  76. Sainsbury F, Thuenemann EC, Lomonossoff GP (2009) pEAQ: versatile expression vectors for easy and quick transient expression of heterologous proteins in plants. Plant Biotechnol 7:682–693CrossRefGoogle Scholar
  77. Saldaña S et al (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(1):42–53. Scholar
  78. Samy AM, Peterson AT (2016) Climate change influences on the global potential distribution of bluetongue virus. PLoS ONE 11(3):e0150489. Scholar
  79. Sathish K et al (2011) Plant expressed EtMIC2 is an effective immunogen in conferring protection against chicken coccidiosis. Vaccine 29(49):9201–9208. Scholar
  80. Sathish K et al (2012) Plant expressed coccidial antigens as potential vaccine candidates in protecting chicken against coccidiosis. Vaccine 30(30):4460–4464. Scholar
  81. Satyavathi V, Prasad V, Khandelwal A, Shaila M, Sita LG (2003) Expression of hemagglutinin protein of rinderpest virus in transgenic pigeon pea [Cajanus cajan (L.) Millsp.] plants. Plant Cell Rep 21(7):651–658
  82. Shirley MW, Smith AL, Tomley FM (2005) The biology of avian Eimeriawith an emphasis on their control by vaccination. Adv Parasitol 60
  83. Shirley MW, Smith AL, Blake DP (2007) Challenges in the successful control of the avian coccidia. Vaccine 25
  84. Shivaramaiah C, Barta JR, Hernandez-Velasco X, Téllez G, Hargis BM (2014) Coccidiosis: recent advancements in the immunobiology of Eimeria species, preventive measures, and teh importance of vaccination as a control tool against these Apicomlexan parasites. Vet Med Res Rep 5:23–34Google Scholar
  85. Song CS et al (1998) Induction of protective immunity in chickens vaccinated with infectious bronchitis virus S1 glycoprotein expressed by a recombinant baculovirus. J Gen Virol 79(4):719–723. Scholar
  86. Sperlova A, Zendulkova D (2011) Bluetongue: a review. Vet Med 56(9):430–452CrossRefGoogle Scholar
  87. Spik K, Shurtleff A, McElroy AK, Guttieri MC, Hooper JW, Schmaljohn C (2006) Immunogenicity of combination DNA vaccines for rift valley fever virus, tick-borne encephalitis virus, Hantaan virus, and Crimean Congo hemorrhagic fever virus. Vaccine 24(21):4657–4666. Scholar
  88. Stewart M et al (2012) Protective efficacy of Bluetongue virus-like and subvirus-like particles in sheep: presence of the serotype-specific VP2, independent of its geographic lineage, is essential for protection. Vaccine 30(12):2131–2139. Scholar
  89. 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:n/a-n/a. Scholar
  90. Thomas C, Young NJ, Heaney J, Collins ME, Brownlie J (2009) Evaluation of efficacy of mammalian and baculovirus expressed E2 subunit vaccine candidates to bovine viral diarrhoea virus. Vaccine 27(17):2387–2393.CrossRefPubMedGoogle Scholar
  91. Tuboly T et al (2000) Immunogenicity of porcine transmissible gastroenteritis virus spike protein expressed in plants. Vaccine 18(19):2023–2028. Scholar
  92. van Drunen LH (2006) Rationale and perspectives on the success of vaccination against bovine herpesvirus-1. Vet Microbiol 113(3–4):275–282. Scholar
  93. van Zyl AR, Meyers AE, Rybicki EP (2016) Transient Bluetongue virus serotype 8 capsid protein expression in Nicotiana benthamiana. Biotechnol Rep 9:15–24. Scholar
  94. Wallace DB, Ellis CE, Espach A, Smith SJ, Greyling RR, Viljoen GJ (2006) Protective immune responses induced by different recombinant vaccine regimes to rift valley fever. Vaccine 24(49–50):7181–7189. Scholar
  95. Whitehouse CA (2004) Crimean-Congo hemorrhagic fever. Antiviral Res 64:145–160CrossRefPubMedGoogle Scholar
  96. Wigdorovitz A et al (2004) Protective lactogenic immunity conferred by an edible peptide vaccine to bovine rotavirus produced in transgenic plants. J Gen Virol 85(7):1825–1832. Scholar
  97. Yang Y et al (2011) Immunogenicity and virus-like particle formation of rotavirus capsid proteins produced in transgenic plants. Sci China Life Sci 54(1):82–89. Scholar
  98. Zhou J-Y et al (2004) Generation of the transgenic potato expressing full-length spike protein of infectious bronchitis virus. J Biotechnol 111(2):121–130. Scholar
  99. Zhou B et al (2010) Oral administration of plant-based rotavirus VP6 induces antigen-specific IgAs, IgGs and passive protection in mice. Vaccine 28(37):6021–6027. Scholar
  100. Zhou ZR, Wang ML, Deng F, Li Tx HuZH, Wang HL (2011) Production of CCHF virus-like particle by a baculovirus-insect cell expression. Virologica Sinica 26:338–346CrossRefPubMedGoogle Scholar
  101. Zientara S, Maclachlan N, Calistri P, Sanchez-Vizcaino J, Savini G (2010) Bluetongue vaccination in Europe. Expert Rev Vaccines 9:989–991CrossRefPubMedGoogle Scholar
  102. Zimmermann J et al (2009) Antibody expressing pea seeds as fodder for prevention of gastrointestinal parasitic infections in chickens. BMC Biotechnol 9(1):79. Scholar

Copyright information

© 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

Personalised recommendations