Abstract
Infectious bursal disease is a widely spread threatening contagious viral infection of chickens that induces major damages to the Bursa of Fabricius and leads to severe immunosuppression in young birds causing significant economic losses for poultry farming. The etiological agent is the infectious bursal disease virus (IBDV), a non-enveloped virus belonging the family of Birnaviridae. At present, the treatment against the spread of this virus is represented by vaccination schedules mainly based on inactivated or live-attenuated viruses. However, these conventional vaccines present several drawbacks such as insufficient protection against very virulent strains and the impossibility to differentiate vaccinated animals from infected ones. To overcome these limitations, in the last years, several studies have explored the potentiality of recombinant subunit vaccines to provide an effective protection against IBDV infection. In this review, we will give an overview of these novel types of vaccines with special emphasis on current state-of-the-art in the use of plants as “biofactories” (plant molecular farming). In fact, plants have been thoroughly and successfully characterized as heterologous expression systems for the production of recombinant proteins for different applications showing several advantages compared with traditional expression systems (Escherichia coli, yeasts and insect cells) such as absence of animal pathogens in the production process, improved product quality and safety, reduction of manufacturing costs, and simplified scale-up.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Al-Natour MQ, Ward LA, Saif YM, Stewart-Brown B, Keck LD (2004) Effect of different levels of maternally derived antibodies on protection against infectious bursal disease virus. Avian Dis 48:177–182. https://doi.org/10.1637/5319
Balke I, Zeltins A (2019) Use of plant viruses and virus-like particles for the creation of novel vaccines. Adv Drug Deliv Rev 145:119–129. https://doi.org/10.1016/j.addr.2018.08.007
Böttcher B, Kiselev NA, Stel'Mashchuk VY, Perevozchikova NA, Borisov AV, Crowther RA (1997) Three-dimensional structure of infectious bursal disease virus determined by electron cryomicroscopy. J Virol 71:325–330
Canto T (2016) Transient expression systems in plants: potentialities and constraints. Adv Exp Med Biol 896:287–301. https://doi.org/10.1007/978-3-319-27216-0_18
Chen K, Cerutti A (2010) Vaccination strategies to promote mucosal antibody responses. Immunity 33:479–491. https://doi.org/10.1016/j.immuni.2010.09.013
Chen Q, Lai H (2015) Gene delivery into plant cells for recombinant protein production. Biomed Res Int 2015:932161. https://doi.org/10.1155/2015/932161
Chen TH, Chen TH, Hu CC, Liao JT, Lee CW, Liao JW, Lin MY, Liu HJ, Wang MY, Lin NS, Hsu YH (2012) Induction of protective immunity in chickens immunized with plant-made chimeric Bamboo mosaic virus particles expressing very virulent infectious bursal disease virus antigen. Virus Res 166:109–115. https://doi.org/10.1016/j.virusres.2012.02.021
Chung SM, Frankman EL, Tzfira T (2005) A versatile vector system for multiple gene expression in plants. Trends Plant Sci 10:357–361. https://doi.org/10.1016/j.tplants.2005.06.001
Coulibaly F, Chevalier C, Gutsche I, Pous J, Navaza J, Bressanelli S, Delmas B, Rey FA (2005) The birnavirus crystal structure reveals structural relationships among icosahedral viruses. Cell 120:761–772. https://doi.org/10.1016/j.cell.2005.01.009
Darteil R, Bublot M, Laplace E, Bouquet JF, Audonnet JC, Rivière M (1995) Herpesvirus of turkey recombinant viruses expressing infectious bursal disease virus (IBDV) VP2 immunogen induce protection against an IBDV virulent challenge in chickens. Virology 211:481–490. https://doi.org/10.1006/viro.1995.1430
Di Bonito P, Grasso F, Mangino G, Massa S, Illiano E, Franconi R, Fanales-Belasio E, Falchi M, Affabris E, Giorgi C (2009) Immunomodulatory activity of a plant extract containing human papillomavirus 16-E7 protein in human monocyte-derived dendritic cells. Int J Immunopathol Pharmacol 22:967–978. https://doi.org/10.1177/039463200902200412
Donini M, Marusic C (2019) Current state-of-the-art in plant-based antibody production systems. Biotechnol Lett 41:335–346. https://doi.org/10.1007/s10529-019-02651-z
Fahey KJ, Erny K, Crooks J (1989) A conformational immunogen on VP-2 of infectious bursal disease virus that induces virus-neutralizing antibodies that passively protect chickens. J Gen Virol 70:1473–1481. https://doi.org/10.1099/0022-1317-70-6-1473
Feng H, SP MD, Fan J, Yang S, Zhao X, Lu Y, Gan Y, Yi X, Chang YF (2017) Phosphorylated radix Cyathulae officinalis polysaccharides act as adjuvant via promoting dendritic cell maturation. Molecules 22:E106. https://doi.org/10.3390/molecules22010106
Fischer R, Stoger E, Schillberg S, Christou P, Twyman RM (2004) Plant-based production of biopharmaceuticals. Curr Opin Plant Biol 7:152–158. https://doi.org/10.1016/j.pbi.2004.01.007
Gómez E, Lucero MS, Chimeno Zoth S, Carballeda JM, Gravisaco MJ, Berinstein A (2013) Transient expression of VP2 in Nicotiana benthamiana and its use as a plant-based vaccine against infectious bursal disease virus. Vaccine 31:2623–2627. https://doi.org/10.1016/j.vaccine.2013.03.064
Hefferon K (2017) Plant virus expression vectors: a powerhouse for global health. Biomedicines 5:E44. https://doi.org/10.3390/biomedicines5030044
Henderson LM (2005) Overview of marker vaccine and differential diagnostic test technology. Biologicals 33:203–209. https://doi.org/10.1016/j.vaccine.2013.03.064
Ignjatovic J, Gould G, Trinidad L, Sapats S (2006) Chicken recombinant antibodies against infectious bursal disease virus are able to form antibody-virus immune complex. Avian Pathol 35:293–301. https://doi.org/10.1080/03079450600823378
Ingrao F, Rauw F, Lambrecht B, van den Berg T (2013) Infectious bursal disease: a complex host-pathogen interaction. Dev Comp Immunol 41:429–438. https://doi.org/10.1016/j.dci.2013.03.017
Iván J, Velhner M, Ursu K, German P, Mató T, Drén CN, Mészáros J (2005) Delayed vaccine virus replication in chickens vaccinated subcutaneously with an immune complex infectious bursal disease vaccine: quantification of vaccine virus by real-time polymerase chain reaction. Can J Vet Res 69:135–142
Jacob SS, Cherian S, Sumithra TG, Raina OK, Sankar M (2013) Edible vaccines against veterinary parasitic diseases–current status and future prospects. Vaccine 31:1879–1885. https://doi.org/10.1016/j.vaccine.2013.02.022
Jackwood DJ (2004) Recent trends in the molecular diagnosis of infectious bursal disease viruses. Anim Health Res Rev 5:313–316. https://doi.org/10.1079/ahr200490
Jackwood DJ (2011) Viral competition and maternal immunity influence the clinical disease caused by very virulent infectious bursal disease virus. Avian Dis 55:398–406. https://doi.org/10.1637/9671-012811-Reg.1
Jackwood DJ, Sommer-Wagner S (2007) Genetic characteristics of infectious bursal disease viruses from four continents. Virology 365:369–375. https://doi.org/10.1016/j.virol.2007.03.046
Komarova TV, Baschieri S, Donini M, Marusic C, Benvenuto E, Dorokhov YL (2010) Transient expression systems for plant-derived biopharmaceuticals. Expert Rev Vaccines 9(8):859–876. https://doi.org/10.1586/erv.10.85
Letzel T, Coulibaly F, Rey FA, Delmas B, Jagt E, van Loon AA, Mundt E (2007) Molecular and structural bases for the antigenicity of VP2 of infectious bursal disease virus. J Virol 81(23):12827–12835. https://doi.org/10.1128/JVI.01501-07
Lico C, Chen Q, Santi L (2008) Viral vectors for production of recombinant proteins in plants. J Cell Physiol 216:366–377. https://doi.org/10.1002/jcp.21423
Lico C, Marusic C, Capuano F, Buriani G, Benvenuto E, Baschieri S (2012) Plant-based vaccine delivery strategies. In: Baschieri S (ed) Innovation in vaccinology: from design, through to delivery and testing. Springer, Berlin, pp 179–203
Liew PS, Hair-Bejo M (2015) Farming of plant-based veterinary vaccines and their applications for disease prevention in animals. Adv Virol 2015:936940. https://doi.org/10.1155/2015/936940
Liu L, Zhang W, Song Y, Wang W, Zhang Y, Wang T, Li K, Pan Q, Qi X, Gao Y, Gao L, Liu C, Zhang Y, Wang Y, He G, Wang X, Cui H (2018) Recombinant Lactococcus lactis co-expressing OmpH of an M cell-targeting ligand and IBDV-VP2 protein provide immunological protection in chickens. Vaccine 36:729–735. https://doi.org/10.1016/j.vaccine.2017.12.027
Lucero MS, Richetta M, Chimeno Zoth S, Jaton J, Pinto S, Canet Z, Berinstein A, Gómez E (2019) Plant-based vaccine candidate against infectious bursal disease: an alternative to inactivated vaccines for breeder hens. Vaccine 37:5203–5210. https://doi.org/10.1016/j.vaccine.2019.07.069
Mahgoub HA, Bailey M, Kaiser P (2012) An overview of infectious bursal disease. Arch Virol 157:2047–5207. https://doi.org/10.1016/j.vaccine.2019.07.069
Makhzoum A, Benyammi R, Moustafa K, Trémouillaux-Guiller J (2014) Recent advances on host plants and expression cassettes' structure and function in plant molecular pharming. Bio Drugs 28:145–159. https://doi.org/10.1007/s40259-013-0062-1
Martinez-Torrecuadrada JL, Saubi N, Pagès-Manté A, Castón JR, Espuña E, Casal JI (2003) Structure-dependent efficacy of infectious bursal disease virus (IBDV) recombinant vaccines. Vaccine 21:3342–3350. https://doi.org/10.1016/s0264-410x(02)00804-6
Müller H, Mundt E, Eterradossi N, Islam MR (2012) Current status of vaccines against infectious bursal disease. Avian Pathol 41:133–139. https://doi.org/10.1080/03079457.2012.661403
Norkunas K, Harding R, Dale J, Dugdale B (2018) Improving agroinfiltration-based transient gene expression in Nicotiana benthamiana. Plant Methods 14:71. https://doi.org/10.1186/s13007-018-0343-2
Oppling V, Müller H, Becht H (1991) Heterogeneity of the antigenic site responsible for the induction of neutralizing antibodies in infectious bursal disease virus. Arch Virol 119:211–223. https://doi.org/10.1007/bf01310671
Peyret H, Lomonossoff GP (2015) When plant virology met Agrobacterium: the rise of the deconstructed clones. Plant Biotechnol J 13:1121–1135. https://doi.org/10.1111/pbi.12412
Pikuła A, Lisowska A, Jasik A, Śmietanka K (2018) Identification and assessment of virulence of a natural reassortant of infectious bursal disease virus. Vet Res 49:89. https://doi.org/10.1186/s13567-018-0586-y
Porta C, Lomonossoff GP (2002) Viruses as vectors for the expression of foreign sequences in plants. Biotechnol Genet Eng Rev 19:245–291. https://doi.org/10.1080/02648725.2002.10648031
Prandini F, Simon B, Jung A, Pöppel M, Lemiere S, Rautenschlein S (2016) Comparison of infectious bursal disease live vaccines and a HVT-IBD vector vaccine and their effects on the immune system of commercial layer pullets. Avian Pathol 45:114–125. https://doi.org/10.1080/03079457.2015.1127891
Rage E, Drissi Touzani C, Marusic C, Lico C, Göbel T, Bortolami A, Bonfante F, Salzano AM, Scaloni A, Fellahi S, El Houadfi M, Donini M, Baschieri S (2019) Functional characterization of a plant-produced infectious bursal disease virus antigen fused to the constant region of avian IgY immunoglobulins. Appl Microbiol Biotechnol 103:7491–7504. https://doi.org/10.1007/s00253-019-09992-9
Rautenschlein S, Kraemer CH, Vanmarcke J, Montiel E (2005) Protective efficacy of intermediate and intermediate plus infectious bursal disease virus (IBDV) vaccines against very virulent IBDV in commercial broilers. Avian Dis 49:231–237. https://doi.org/10.1637/7310-112204R
Richetta M, Gómez E, Lucero MS, Chimeno Zoth S, Gravisaco MJ, Calamante G, Berinstein A (2017) Comparison of homologous and heterologous prime-boost immunizationscombining MVA-vectored and plant-derived VP2 as a strategy against IBDV. Vaccine 35:142–148. https://doi.org/10.1016/j.vaccine.2016.11.029
Rong J, Jiang T, Cheng T, Shen M, Du Y, Li S, Wang S, Xu B, Fan G (2007) Large-scale manufacture and use of recombinant VP2 vaccine against infectious bursal disease in chickens. Vaccine 25:7900–7908. https://doi.org/10.1016/j.vaccine.2007.09.006
Saugar I, Luque D, Oña A, Rodríguez JF, Carrascosa JL, Trus BL, Castón JR (2005) Structural polymorphism of the major capsid protein of a double-stranded RNA virus: an amphipathic alpha helix as a molecular switch. Structure 13:1007–1017. https://doi.org/10.1016/j.str.2005.04.012
Sheludko YV (2008) Agrobacterium-mediated transient expression as an approach to production of recombinant proteins in plants. Recent Pat Biotechnol 2:198–208. https://doi.org/10.2174/187220808786241033
Taghavian O (2013) Expression and characterization of infectious bursal disease virus protein for poultry vaccine development and application in nanotechnology. PhD Thesis dissertation. https://doi.org/10.13140/2.1.3393.1846
Taghavian O, Spiegel H, Hauck R, Hafez HM, Fischer R, Schillberg S (2013) Protective oral vaccination against infectious bursal disease virus using the major viral antigenic protein VP2 produced in Pichia pastoris. PLoS One 8:e83210. https://doi.org/10.1371/journal.pone.0083210
van den Berg TP, Eterradossi N, Toquin D, Meulemans G (2000) Infectious bursal disease (Gumboro disease). Rev Sci Tech 19:509–543. https://doi.org/10.20506/rst.19.2.1227
Vermij P, Waltz E (2006) News in brief: USDA approves the first plant-based vaccine. Nat Biotechnol 24:233–234. https://doi.org/10.1038/nbt0306-233
Whitfill CE, Haddad EE, Ricks CA, Skeeles JK, Newberry LA, Beasley JN, Andrews PD, Thoma JA, Wakenell PS (1995) Determination of optimum formulation of a novel infectious bursal disease virus (IBDV) vaccine constructed by mixing bursal disease antibody with IBDV. Avian Dis 39:687–699
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 26:787–792. https://doi.org/10.1023/b:bile.0000025878.30350.d5
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 48:663–668. https://doi.org/10.1637/7074
Wu J, Yu L, Li L, Hu J, Zhou J, Zhou X (2007) Oral immunization with transgenic rice seeds expressing VP2 protein of infectious bursal disease virus induces protective immune responses in chickens. Plant Biotechnol J 5:570–578. https://doi.org/10.1111/j.1467-7652.2007.00270.x
Xu J, Ge X, Dolan MC (2011) Towards high-yield production of pharmaceutical proteins with plant cell suspension cultures. Biotechnol Adv 29:278–299. https://doi.org/10.1016/j.biotechadv.2011.01.002
Xu J, Zhang N (2014) On the way to commercializing plant cell culture platform for biopharmaceuticals: present status and prospect. Pharm Bioprocess 2:499–518. https://doi.org/10.4155/pbp.14.32
Yang Y, Wei K, Yang S, Li B, Zhang Y, Zhu F, Wang D, Chi S, Jiang X, Zhu R (2015) Co-adjuvant effects of plant polysaccharide and propolis on chickens inoculated with Bordetella avium inactivated vaccine. Avian Pathol 44:248–253. https://doi.org/10.1080/03079457.2015.1040372
Zachar T, Popowich S, Goodhope B, Knezacek T, Ojkic D, Willson P, Ahmed KA, Gomis S (2016) A 5-year study of the incidence and economic impact of variant infectious bursal disease viruses on broiler production in Saskatchewan, Canada. Can J Vet Res 80:255–261
Zavala G, Cheng S (2006) Detection and characterization of avian leukosis virus in Marek’s disease vaccines. Avian Dis 50:209–215. https://doi.org/10.1637/7444-092405R.1
Funding
This study was funded by AVIAMED project through the ERANET ARIMNet2 2015 Call by the following funding agencies: Italian Ministry of Agricultural, Food and Forestry Policies (MIPAAF) and Ministry of Higher Education, Scientific Research and Professional Training of Morocco (MESRSFC). ARIMNet2 (ERA-NET) has received funding from the European Union’s Seventh Framework Programme for research, technological development, and demonstration under grant agreement no. 618127/182.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
This article does not contain any studies with human participants or animals performed by any of the authors.
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Rage, E., Marusic, C., Lico, C. et al. Current state-of-the-art in the use of plants for the production of recombinant vaccines against infectious bursal disease virus. Appl Microbiol Biotechnol 104, 2287–2296 (2020). https://doi.org/10.1007/s00253-020-10397-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00253-020-10397-2