Infectious Bursal Disease Virus

  • Evangelina Gómez
  • María Soledad Lucero
  • Matías Richetta
  • Silvina Chimeno Zoth
  • Analía BerinsteinEmail author


Infectious bursal disease is an acute, highly contagious, immunosuppressive disease that affects young birds causing important economic losses in the poultry industry. Its etiological agent is the Infectious bursal disease virus (IBDV), a non-enveloped bi-segmented double stranded RNA virus which belongs to the Genus Avibirnavirus from the Family Birnaviridae. Currently, control of IBDV is normally achieved by vaccination programs with inactivated and live attenuated viruses. However, conventional vaccines have a number of disadvantages due to their viral nature and, in many cases, fail to provide sufficient protection against very virulent and variant strains of IBDV. Several new vaccines have been developed as alternatives to solve these problems. Among these rationally designed vaccines live viral-vectored, immune complex and subunit vaccines are found. In this chapter, the contribution of these new technologies to the field will be addressed, with special focus on plant-made vaccines candidates against IBDV. The rationale, efficacy, and yield of these plant-based developments, as well as the comparison to established vaccines or alternatives will be discussed.


Molecular farming IBDV Chicken VP2 Recombinant vaccine Transient expression 


  1. Ahmed Z, Akhter S (2003) Role of maternal antibodies in protection against infectious bursal disease in commercial broilers. Int J Poult Sci 2:251–255. Scholar
  2. Alkhalaf AN (2009) Detection of variant strains of infectious bursal disease virus in broiler flocks in Saudi Arabia using antigen capture enzyme-linked immunosorbent assay. Pak Vet J 29:161–164Google Scholar
  3. Alkie TN, Rautenschlein S (2016) Infectious bursal disease virus in poultry: current status and future prospects. Vet Med Res Reports 7:9–18Google Scholar
  4. Aricibasi M, Jung A, Heller DE, Rautenschlein S (2010) Differences in genetic background influence the induction of innate and acquired immune responses in chickens depending on the virulence of the infecting infectious bursal disease virus (IBDV) strain. Vet Immunol Immunopathol 135:79–92. Scholar
  5. Arnold M, Durairaj V, Mundt E et al (2012) Protective vaccination against infectious bursal disease virus with whole recombinant Kluyveromyces lactis yeast expressing the viral VP2 subunit. PLoS ONE 7:e42870. Scholar
  6. Bayliss CD, Spies U, Shaw K et al (1990) A comparison of the sequences of segment A of four infectious bursal disease virus strains and identification of a variable region in VP2. J Gen Virol 71:1303–1312. Scholar
  7. Brandt M, Yao K, Liu M et al (2001) Molecular determinants of virulence, cell tropism, and pathogenic phenotype of infectious bursal disease virus. J Virol 75:11974–11982CrossRefPubMedPubMedCentralGoogle Scholar
  8. Burkhardt E, Müller H (1987) Susceptibility of chicken blood lymphoblasts and monocytes to infectious bursal disease virus (IBDV). Arch Virol 94:297–303CrossRefPubMedGoogle Scholar
  9. Caballero JM, Garzón A, González-Cintado L et al (2012) Chimeric infectious bursal disease virus-like particles as potent vaccines for eradication of established HPV-16 E7–dependent tumors. PLoS ONE 7:e52976CrossRefGoogle Scholar
  10. Chen Q, Lai H (2015) Gene Delivery into Plant Cells for Recombinant Protein Production. Biomed Res Int 2015:1–10. Scholar
  11. Chen F, Liu J, Yan Z et al (2012a) Complete Genome Sequence Analysis of a Natural Reassortant Infectious Bursal Disease Virus in China. J Virol 86:11942–11943. Scholar
  12. Chen T-H, Chen T-H, Hu C-C et al (2012b) 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 166:109–115CrossRefPubMedGoogle Scholar
  13. Coulibaly F, Chevalier C, Gutsche I et al (2005) The birnavirus crystal structure reveals structural relationships among icosahedral viruses. Cell 120:761–772. Scholar
  14. Coulibaly F, Chevalier C, Delmas B, Rey FA (2010) Crystal structure of an Aquabirnavirus particle: insights into antigenic diversity and virulence determinism. J Virol 84:1792–1799CrossRefPubMedGoogle Scholar
  15. Da Costa B, Delmas B, Lejal N, Huet J-C (2000) Role of Ser-652 and Lys-692 in the protease activity of infectious bursal disease virus VP4 and identification of its substrate cleavage sites. J Gen Virol 81:983–992. Scholar
  16. Delgui LR, Oña A, Gutiérrez S et al (2009) The capsid protein of infectious bursal disease virus contains a functional α4β1 integrin ligand motif. Virology 386:360–372CrossRefPubMedGoogle Scholar
  17. Delgui LR, Rodriguez JF, Colombo MI (2013) The endosomal pathway and the golgi complex are involved in the infectious bursal disease virus life cycle. J Virol 87:8993–9007. Scholar
  18. Delrue I, Verzele D, Madder A, Nauwynck HJ (2012) Inactivated virus vaccines from chemistry to prophylaxis: merits, risks and challenges. Expert Rev Vaccines 11:695–719. Scholar
  19. Dey S, Upadhyay C, Mohan CM et al (2009) Formation of subviral particles of the capsid protein VP2 of infectious bursal disease virus and its application in serological diagnosis. J Virol Methods 157:84–89CrossRefPubMedGoogle Scholar
  20. Dobos P, Hill BJ, Hallett R et al (1979) Biophysical and biochemical characterization of five animal viruses with bi-segemented double stranded RNA genomes. J Virol 32:593–605PubMedPubMedCentralGoogle Scholar
  21. El-Yuguda AD, Wachida N, Baba SS (2007) Interference of infectious bursal diseases (IBD) virus and vaccine with the immune responses of Guinea fowls to newcastle disease Lasota vaccinationGoogle Scholar
  22. Eterradossi N, Saif YM (2008) Infectious Bursal Disease. Diseases of poultry, 12th edn. Blackwell Publishing, Iowa, USA, pp 185–209Google Scholar
  23. Galloux M, Libersou S, Morellet N et al (2007) Infectious bursal disease virus, a non-enveloped virus, possesses a capsid-associated peptide that deforms and perforates biological membranes. J Biol Chem 282:20774–20784CrossRefPubMedGoogle Scholar
  24. Garriga D, Querol-Audí J, Abaitua F et al (2006) The 2.6-Angstrom structure of infectious bursal disease virus-derived T = 1 particles reveals new stabilizing elements of the virus capsid. J Virol 80:6895–6905CrossRefPubMedPubMedCentralGoogle Scholar
  25. Gelb J, Jackwood DJ, Brannick EM, Ladman BS (2016) Efficacy of recombinant HVT-IBD vaccines administered to broiler chicks from a single breeder flock at 30 and 60 weeks of age. Avian Dis 60:603–612. Scholar
  26. Ghafari S, Seyfiabad Shapouri MR, Moatamedi H et al (2010) Cloning and secretory expression of VP2 gene of infectious bursal disease virus in eukaryotic cells. Iran J Vet Res 11:72–77Google Scholar
  27. Gleba Y, Klimyuk V, Marillonnet S (2005) Magnifection—a new platform for expressing recombinant vaccines in plants. Vaccine 23:2042–2048. Scholar
  28. Gómez E, Lucero MS, Chimeno Zoth S et al (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. Scholar
  29. Haddad EE, Whitfill CE, Avakian AP et al (1997) Efficacy of a novel infectious bursal disease virus immune complex vaccine in broiler chickens. Avian Dis 41:882–889CrossRefPubMedGoogle Scholar
  30. Harris J (2010) Characterization of infectious bursal disease viruses isolated from commercial chickens. University of DelawareGoogle Scholar
  31. He C-Q, Ma L-Y, Wang D et al (2009) Homologous recombination is apparent in infectious bursal disease virus. Virology 384:51–58. Scholar
  32. Ho J-Y, Lee L-H, Lin Y-C et al (2010) Vaccine development through terminal deletions of an infectious bursal disease virus protein 2 precursor variant. Process Biochem 45:786–793CrossRefGoogle Scholar
  33. Ingrao F, Rauw F, Lambrecht B, Van den Berg TP (2013) Infectious bursal disease: a complex host-pathogen interaction. Dev Comp Immunol 41:429–438. Scholar
  34. Inoue M, Fukuda M, Miyano K (1994) Thymic lesions in chicken infected with infectious bursal disease virus. Avian Dis 38(4):839–846CrossRefPubMedGoogle Scholar
  35. Ismail NM, Saif YM, Moorhead PD (1988) Lack of pathogenicity of five serotype 2 infectious bursal disease viruses in chickens. Avian Dis 32:757–759. Scholar
  36. Jackwood DJ (2012) Molecular epidemiologic evidence of homologous recombination in infectious bursal disease viruses. Avian Dis 56:574–577. Scholar
  37. Jackwood DJ (2013) Multivalent virus-like–particle vaccine protects against classic and variant infectious bursal disease viruses. Avian Dis 57:41–50. Scholar
  38. Jackwood DJ, Saif YM, Moorhead PD (1985) Immunogenicity and antigenicity of infectious bursal disease virus serotypes I and II in chickens. Avian Dis 29:1184–1194. Scholar
  39. Jin T, Wang J, Zhu X et al (2015) A new transient expression system for large-scale production of recombinant proteins in plants based on air-brushing an agrobacterium suspension. Biotechnol Reports 6:36–40. Scholar
  40. Kegne T, Chanie M (2014) Review on the incidence and pathology of infectious bursal disease. Br J Poult Sci 3:68–77. Scholar
  41. Kelemen M, Forgách K, Iván J et al (2000) Pathological and immunological study of an in ovo complex vaccine against infectious bursal disease. Acta Vet Hung 48:443–454CrossRefPubMedGoogle Scholar
  42. Khatri M, Palmquist JM, Cha RM, Sharma JM (2005) Infection and activation of bursal macrophages by virulent infectious bursal disease virus. Virus Res 113:44–50CrossRefPubMedGoogle Scholar
  43. Kim I-J, Sharma JM (2000) IBDV-induced bursal T lymphocytes inhibit mitogenic response of normal splenocytes. Vet Immunol Immunopathol 74:47–57CrossRefPubMedGoogle Scholar
  44. Kumar K, Singh KC, Prasad CB (2000) Immune responses to intermediate strain IBD vaccine at different levels of maternal antibody in broiler chickens. Trop Anim Health Prod 32:357–360CrossRefPubMedGoogle Scholar
  45. Kurukulsuriya S, Ahmed KA, Ojkic D et al (2016) Circulating strains of variant infectious bursal disease virus may pose a challenge for antibiotic-free chicken farming in Canada. Res Vet Sci 108:54–59. Scholar
  46. Lee C-C, Kim B-S, Wu CC, Lin TL (2015) Bursal transcriptome of chickens protected by DNA vaccination versus those challenged with infectious bursal disease virus. Arch Virol 160:69–80. Scholar
  47. Licciardi PV, Underwood JR (2011) Plant-derived medicines: a novel class of immunological adjuvants. Int Immunopharmacol 11:390–398. Scholar
  48. Lin T-W, Lo C-W, Lai S-Y et al (2007) Chicken heat shock protein 90 is a component of the putative cellular receptor complex of infectious bursal disease virus. J Virol 81:8730–8741CrossRefPubMedPubMedCentralGoogle Scholar
  49. Lucero MS, Gómez E, Carballeda JM et al (2012) Recombinant vaccines and infectious bursal disease virus. CAB Rev Perspect Agric Vet Sci Nutr Nat Resour 7:215. Scholar
  50. Lucero MS, Gómez E, Richetta M et al (2016) Effect of different routes of inoculation on plant-derived VP2 immunogenicity and ability to confer protection against infectious bursal diseaseGoogle Scholar
  51. Luo J, Zhang H, Teng M et al (2010) Surface IgM on DT40 cells may be a component of the putative receptor complex responsible for the binding of infectious bursal disease virus. Avian Pathol 39:359–365CrossRefPubMedGoogle Scholar
  52. Luque D, Rivas G, Alfonso C et al (2009) Infectious bursal disease virus is an icosahedral polyploid dsRNA virus. Proc Natl Acad Sci 106:2148–2152CrossRefPubMedGoogle Scholar
  53. Maas RA, Venema S, Oei HL et al (2001) Efficacy of inactivated infectious bursal disease (IBD) vaccines: comparison of serology with protection of progeny chickens against IBD virus strains of varying virulence. Avian Pathol 30:345–354. Scholar
  54. Mason HS, Herbst-Kralovetz MM (2012) Plant-derived antigens as mucosal vaccines. In: Kozlowski PA (ed) Mucosal vaccines: modern concepts, strategies, and challenges. Springer, Berlin, Heidelberg, pp 101–120Google Scholar
  55. Mazariegos LA, Lukert PD, Brown J (1990) Pathogenicity and immunosuppressive properties of infectious bursal disease “intermediate” strains. Avian Dis 34:203–208CrossRefPubMedGoogle Scholar
  56. Méndez F, Romero N, Cubas LL et al (2017) Non-lytic egression of infectious bursal disease virus (IBDV) particles from infected cells. PLoS ONE 12:e0170080. Scholar
  57. Mertens J, Casado S, Mata CP et al (2015) A protein with simultaneous capsid scaffolding and dsRNA-binding activities enhances the birnavirus capsid mechanical stability. Sci Rep 5:13486. Scholar
  58. Morgan MM, Macreadie IG, Harley VR et al (1988) Sequence of the small double-stranded RNA genomic segment of infectious bursal disease virus and its deduced 90-kDa product. Virology 163:240–242. Scholar
  59. Müller H, Scholtissek C, Becht H (1979) The genome of infectious bursal disease virus consists of two segments of double-stranded RNA. J Virol 31:584–589PubMedPubMedCentralGoogle Scholar
  60. Müller H, Mundt E, Eterradossi N, Islam MR (2012) Current status of vaccines against infectious bursal disease. Avian Pathol 41:133–139. Scholar
  61. Mundt E, Beyer J, Müller H (1995) Identification of a novel viral protein in infectious bursal disease virus-infected cells. J Gen Virol 76:437–443CrossRefPubMedGoogle Scholar
  62. Naderi S, Fakheri B (2015) Overview of plant-based vaccines. Res J Fish Hydrobiol 10:275–289Google Scholar
  63. Oláh I, Nagy N, Vervelde L (2013) Structure of the avian lymphoid system. In: Schat K, Kaspers B, Kaiser P (eds) Avian immunology, 2nd edn. Elsevier, San Diego, CA, pp 11–44Google Scholar
  64. Pascual E, Mata CP, Gómez-Blanco J et al (2015) Structural basis for the development of avian virus capsids that display influenza virus proteins and induce protective immunity. J Virol 89:2563–2574CrossRefPubMedGoogle Scholar
  65. Perozo F, Villegas P, Fernandez R et al (2009) Efficacy of single dose recombinant herpesvirus of Turkey infectious bursal disease virus (IBDV) vaccination against a variant IBDV strain. Avian Dis 53:624–628. Scholar
  66. Peyret H, Lomonossoff GP (2013) The pEAQ vector series: the easy and quick way to produce recombinant proteins in plants. Plant Mol Biol 83:51–58. Scholar
  67. Pitcovski J, Levi BZ, Maray T et al (1999) Failure of viral protein 3 of infectious bursal disease virus produced in prokaryotic and eukaryotic expression systems to protect chickens against the disease. Avian Dis 43(1):8–15CrossRefPubMedGoogle Scholar
  68. Pitcovski J, Gutter B, Gallili G et al (2003) Development and large-scale use of recombinant VP2 vaccine for the prevention of infectious bursal disease of chickens. Vaccine 21:4736–4743CrossRefPubMedGoogle Scholar
  69. Prandini F, Simon B, Jung A et al (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. Scholar
  70. Qi X, Gao H, Gao Y et al (2009) Naturally occurring mutations at residues 253 and 284 in VP2 contribute to the cell tropism and virulence of very virulent infectious bursal disease virus. Antiviral Res 84:225–233CrossRefPubMedGoogle Scholar
  71. Raja P, Senthilkumar TMA, Parthiban M et al (2016) Complete genome sequence analysis of a naturally reassorted infectious bursal disease virus from India. Genome Announc 4:e00709–16. Scholar
  72. Rautenschlein S, Ch Kraemer H, 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. Scholar
  73. Remond M, Da Costa B, Riffault S et al (2009) Infectious bursal disease subviral particles displaying the foot-and-mouth disease virus major antigenic site. Vaccine 27:93–98CrossRefPubMedGoogle Scholar
  74. Richetta M, Gómez E, Lucero MS et al (2017) Comparison of homologous and heterologous prime-boost immunizations combining MVA-vectored and plant-derived VP2 as a strategy against IBDV. Vaccine 35:142–148CrossRefPubMedGoogle Scholar
  75. Rodenberg J, Sharma JM, Belzer SW et al (1994) Flow cytometric analysis of B cell and T cell subpopulations in specific-pathogen-free chickens infected with infectious bursal disease virus. Avian Dis 38(1):16–21CrossRefPubMedGoogle Scholar
  76. Rogel A, Benvenisti L, Sela I et al (2003) Vaccination with E. coli recombinant empty viral particles of infectious bursal disease virus (IBDV) confer protection. Virus Genes 27:169–175CrossRefPubMedGoogle Scholar
  77. Rong J, Jiang T, Cheng T et al (2007) Large-scale manufacture and use of recombinant VP2 vaccine against infectious bursal disease in chickens. Vaccine 25:7900–7908. Scholar
  78. Saif YM (2004) Control of infectious bursal disease virus by vaccination. Dev Biol (Basel) 119:143–146Google Scholar
  79. 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 7:682–693. Scholar
  80. Sapats SI, Ignjatovic J (2000) Antigenic and sequence heterogeneity of infectious bursal disease virus strains isolated in Australia. Arch Virol 145:773–785. Scholar
  81. Sharma JM, Kim I-J, Rautenschlein S, Yeh HY (2000) Infectious bursal disease virus of chickens: pathogenesis and immunosuppression. Dev Comp Immunol 24:223–235. Scholar
  82. Snyder DB, Vakharia VN, Savage PK (1992) Naturally occurring-neutralizing monoclonal antibody escape variants define the epidemiology of infectious bursal disease viruses in the United States. Arch Virol 127:89–101. Scholar
  83. Taghavian O, Spiegel H, Hauck R et al (2013) Protective oral vaccination against infectious bursal disease virus using the major viral antigenic protein VP2 produced in Pichia pastoris. PLoS ONE. Scholar
  84. Tippenhauer M, Heller DE, Weigend S, Rautenschlein S (2013) The host genotype influences infectious bursal disease virus pathogenesis in chickens by modulation of T cells responses and cytokine gene expression. Dev Comp Immunol 40:1–10. Scholar
  85. Van den Berg TP (2000) Acute infectious bursal disease in poultry: a review. Avian Pathol 29:175–194. Scholar
  86. van den Berg TP1, Eterradossi N, Toquin D, Meulemans G (2000) Infectious bursal disease (Gumboro disease). Rev Sci Tech 19(2):509–543Google Scholar
  87. van Loon AAMW, De Haas N, Mundt E (2002) Alteration of amino acids in VP2 of very virulent infectious bursal disease virus results in tissue culture adaptation and attenuation in chickens. J Gen Virol 83:121–129. Scholar
  88. von Einem UI, Gorbalenya AE, Schirrmeier H et al (2004) VP1 of infectious bursal disease virus is an RNA-dependent RNA polymerase. J Gen Virol 85:2221–2229. Scholar
  89. Whetzel PL, Jackwood DJ (1995) Comparison of neutralizing epitopes among infectious bursal disease viruses using radioimmunoprecipitation. Avian Dis 39(3):499–506CrossRefPubMedGoogle Scholar
  90. Wu H, Singh NK, Locy RD et al (2004a) Expression of immunogenic VP2 protein of infectious bursal disease virus in Arabidopsis thaliana. Biotechnol Lett 26:787–792CrossRefPubMedGoogle Scholar
  91. Wu H, Singh NK, Locy RD et al (2004b) Immunization of chickens with VP2 protein of infectious bursal disease virus expressed in Arabidopsis Thaliana. Avian Dis 48:663–668. Scholar
  92. Wu J, Yu L, Li L et al (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. Scholar
  93. Wu Y, Hong L, Ye J et al (2009) The VP5 protein of infectious bursal disease virus promotes virion release from infected cells and is not involved in cell death. Arch Virol 154:1873–1882. Scholar
  94. Yamaguchi T, Setiyono A, Kobayashi M et al (2000) Infectious bursal disease live vaccines: changes in the virus population during serial passage in chickens and chicken embryo fibroblast cells. Avian Dis 44:284. Scholar
  95. Yip CW, Hon CC, Zeng F, Leung FCC (2012) Cell culture-adapted IBDV uses endocytosis for entry in DF-1 chicken embryonic fibroblasts. Virus Res 165:9–16CrossRefPubMedGoogle Scholar
  96. Zachar T, Popowich S, Goodhope B et al (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 80:255–261PubMedPubMedCentralGoogle Scholar
  97. Zhao S, Jia Y, Han D et al (2016) Influence of the structural development of bursa on the susceptibility of chickens to infectious bursal disease virus. Poult Sci 95:2786–2794. Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Evangelina Gómez
    • 1
    • 2
  • María Soledad Lucero
    • 1
  • Matías Richetta
    • 1
  • Silvina Chimeno Zoth
    • 1
    • 2
  • Analía Berinstein
    • 1
    • 2
    Email author
  1. 1.Instituto de Biotecnología, CICVyA, INTABuenos AiresArgentina
  2. 2.CONICETBuenos AiresArgentina

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