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New generation of African horse sickness virus vaccines based on structural and molecular studies of the virus particles

  • P. Roy
  • G. Sutton
Conference paper

Summary

African horse sickness virus (AHSV) is a member of the genus Orbivirus, which also includes bluetongue virus (BTV) and epizootic haemorrhagic disease (EHDV) virus. These orbiviruses have similar morphological and biochemical properties, with distinctive pathobiological properties and host ranges. Sequencing studies of the capsid proteins have revealed evolutionary relationships between these viruses. Biochemical studies of the viruses together with the expression of individual proteins and protein complexes have resulted in the development of new generation vaccines. Baculovirus expressed AHSV VP2 provides protection against death caused by AHSV challenge. Similarly, BTV VP2 alone elicits protective neutralising antibodies against BTV in sheep, which is enhanced in the presence of VP5. Recent developments in biotechnology (multiple gene expression baculovirus systems) have made it possible to synthesise orbivirus particles that biochemically and immunologically mimic authentic virions but lack the genetic material. Particle doses as low as 10 μg elicit responses that are sufficient to protect sheep 15 months post vaccination, against virulent virus challenge. Moreover, knowledge of the three dimensional structure of these particles enables us to engineer them to deliver multiple foreign peptide components representing other viral epitopes (e.g. foot and mouth disease virus and influenza virus) in order to elicit protective immunity.

Keywords

Recombinant Baculovirus Major Capsid Protein Neutralize Antibody Titer Recombinant Baculoviruses Bluetongue Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Basak AK, Stuart DI, Roy P (1992) Preliminary crystallographic study of bluetongue virus capsid protein VP7. J Mol Biol 228: 687–689PubMedCrossRefGoogle Scholar
  2. 2.
    Basak AK, Grimes, JM, Gouet P, Roy P, Stuart DI (1997) Structures of orbivirus VP7: implications for the role of this protein in the viral life cycle. Structure 5: 871–883PubMedCrossRefGoogle Scholar
  3. 3.
    Belyaev AS, Roy P (1992) Presentation of hepatitis B virus preS2 epitope on bluetongue virus core-like, particles. Virology 190: 840–844PubMedCrossRefGoogle Scholar
  4. 4.
    Belyaev AS, Roy P (1993) Development of baculovirus triple and quadruple expression vectors: co-expression of three or four bluetongue virus proteins and the synthesis of bluetongue virus-like particles in insect cells. Nucleic Acids Res 21: 1219–1223PubMedCrossRefGoogle Scholar
  5. 5.
    Belyaev AS, Hails RS, Roy P (1992) High-level expression of five foreign genes by a single recombinant baculovirus. Gene 156: 229–233CrossRefGoogle Scholar
  6. 6.
    Bishop DHL (1992) Baculovirus expression vectors. Semin Virol 3: 253–264Google Scholar
  7. 7.
    Burroughs JN, O’Hara RS, Smale CJ, Hamblin C, Walton A, Armstrong R, Mertens PPC (1994) Purification and properties of virus particles, infectious sub viral particles, cores and VP7 crystals of African horse sickness virus serotype 9. J Gen Virol 75: 1849–1857PubMedCrossRefGoogle Scholar
  8. 8.
    Chuma T, LeBlois H, Sanchez-Vizcaino JM, Diaz-Laviada M, Roy P (1992) Expression of the major core antigen VP7 of African horsesickness virus by a recombinant baculovirus and its use as a group-specific diagnostic reagent. J Gen Virol 73: 925–931PubMedCrossRefGoogle Scholar
  9. 9.
    French TJ, Roy P (1990) Synthesis of bluetongue virus ( BTV) core-like particles by a recombinant baculovirus expressing the two major structural core proteins of BTV. J Virol 64: 1530–1536PubMedGoogle Scholar
  10. 10.
    French TJ, Marshall JA, Roy P (1990) Assembly of double-shelled, virus-like particles of bluetongue virus by the simultaneous expression of four structural proteins. J Virol 64: 5695–5700PubMedGoogle Scholar
  11. 11.
    Fukusho A, Yu Y, Yamaguchi S, Roy P (1989) Completion of the sequence of blue-tongue virus serotype 10 by the characterization of the structural protein, VP6, and a non-structural protein, NS2. J Gen Virol 70: 1677–1689PubMedCrossRefGoogle Scholar
  12. 12.
    Grimes JM, Jakana J, Ghosh M, Basak AK, Roy P, Chiu W, Stuart DI, Prasad BVV (1994) An atomic model of the outer layer of the bluetongue virus core derived from X-ray crystallography and electron microscopy. Structure 5: 885–893CrossRefGoogle Scholar
  13. 13.
    Grimes J, Basak, AK, Roy P, Stuart D (1995) The crystal structure of bluetongue virus VP7. Nature 373: 167–170PubMedCrossRefGoogle Scholar
  14. 14.
    Hewat EA, Booth TF, Roy P (1992) Structure of bluetongue virus particle by cryoelectron microscopy. J Struct Biol 109: 61–69PubMedCrossRefGoogle Scholar
  15. 15.
    Hewat EA, Booth TF, Loudon PT, Roy P (1992) 3-D reconstruction of bluetongue virus core-like particles by cryo-electron microscopy. Virology 189: 10–20PubMedCrossRefGoogle Scholar
  16. 16.
    Hirasawa T, Roy P (1990) The complete nucleotide sequence of VP5 of a strain of bluetongue virus of serotype 2 isolated in the USA reveals its close relationship with a virus of serotype 1 isolated in Australia. Virus Res 15: 107–112PubMedCrossRefGoogle Scholar
  17. 17.
    Huismans H, Van Der Walt NT, Cloete M, Erasmus BJ (1987) Isolation of a capsid protein of bluetongue virus that induces a protective immune response in sheep. Virology 157: 172–179PubMedCrossRefGoogle Scholar
  18. 18.
    Inumaru S, Roy P (1987) Production and characterisation of the neutralisation antigen VP2 of bluetongue virus serotype 10 using a baculovirus expression vector. Virology 157: 472–479PubMedCrossRefGoogle Scholar
  19. 19.
    Iwata H, Chuma T, Roy P (1992) Characterisation of genes encoding two of the major capsid proteins of epizootic haemorrhagic disease virus indicates a close genetic relationship to bluetongue virus. J Gen Virol 73: 915–924PubMedCrossRefGoogle Scholar
  20. 20.
    Iwata H, Hirasawa T, Roy P (1991) Complete nucleotide sequence of segment 6 of epizootic haemorrhagic disease virus; the outer capsid protein VP5 is homologous to that of bluetongue virus. Virus Res 20: 273–281PubMedCrossRefGoogle Scholar
  21. 21.
    Iwata H, Yamagawa M, Roy P (1992) Evolutionary relationships among the gnat-transmitted orbiviruses that cause African horsesickness, bluetongue and epizootic hemorrhagic disease as evidenced by their capsid proteins. Virology 191: 251–261PubMedCrossRefGoogle Scholar
  22. 22.
    LeBlois H, Roy P (1993) A single point mutation in the VP7 major core protein of bluetongue virus prevents the formation of core-like particles. J Virol 67: 353–359Google Scholar
  23. 23.
    LeBlois H, Fayard B, Urakawa T, Roy P (1991) Synthesis and characterisation of chimaeric particles between epizootic haemorrhagic disease virus and bluetongue virus: functional domains are conserved on the VP3 protein. J Virol 65: 4821–4831Google Scholar
  24. 24.
    Loudon PT, Roy P (1991) Assembly of five bluetongue virus proteins expressed by recombinant baculoviruses: inclusion of the largest protein VP1 in the core and virus-like particles. Virology 180: 798–802PubMedCrossRefGoogle Scholar
  25. 25.
    Loudon PT, Roy P (1992) Interaction of nucleic acids with core-like and subcore-like particles of bluetongue virus. Virology 191: 231–236PubMedCrossRefGoogle Scholar
  26. 26.
    Loudon PT, Hirasawa T, Oldfield S, Murphy M, Roy P (1991) Expression of outer capsid protein VP5 of two bluetongue viruses, and synthesis of chimeric double-shelled virus-like particles using combinations of recombinant baculoviruses. Virology 182: 793–801PubMedCrossRefGoogle Scholar
  27. 27.
    Martinez-Torrecuadrada J, Iwata H, Venteo A, Casal I, Roy P (1994) Expression and characterisation of the two outercapsid proteins of African horsesickness virus. The role of VP2 in virus neutralisation. Virology 202: 348–359PubMedCrossRefGoogle Scholar
  28. 28.
    Monastyrskaya K, Staeuber N, Sutton G, Roy P (1997) Effects of domain-switching and site-directed mutagenesis on the properties and functions of the VP7 proteins of two orbiviruses. Virology 237: 217–227PubMedCrossRefGoogle Scholar
  29. 29.
    O’Reilly DR, Miller LK, Luckow VA (1992) (eds) Baculovirus expression vectors: a laboratory manual. WH Freeman, LondonGoogle Scholar
  30. 30.
    Oldfield S, Hirasawa T, Roy P (1990) Sequence conservation of the outer capsid protein, VP5, of bluetongue virus, a contrasting feature to the outer capsid protein VP2. J Gen Virol 72: 449–451CrossRefGoogle Scholar
  31. 31.
    Prasad BVV, Yamaguchi S, Roy P (1992) Three-dimensional structure of single-shelled BTV. J Virol 66: 2135–2142PubMedGoogle Scholar
  32. 32.
    Roy P, Gorman BM (1990) Bluetongue viruses. Curr Top Microbiol Immunol 162Google Scholar
  33. 33.
    Roy P, Bishop DHL, 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
  34. 34.
    Roy P, Callis J, Erasmus BJ (1994) Protection of sheep against bluetongue disease after vaccination with core-like and virus-like particles: evidence for homologous and partial heterologous protection. In: Proceedings for 97th Annual Meeting, USA Health Association. La Vegas, pp 88–97Google Scholar
  35. 35.
    Roy P, French TJ, Erasmus BJ (1992) Protective efficacy of virus-like particles for bluetongue disease. Vaccine 10: 28–32PubMedCrossRefGoogle Scholar
  36. 36.
    Roy P, Hirasawa T, Fernandez M, Blinov VM, Sanchez-Vizcaino JM (1991) The complete sequence of the group-specific antigen, VP7, of African horsesickness disease virus serotype 4 reveals a close relationship to bluetongue virus. J Gen Virol 72: 1237–1241PubMedCrossRefGoogle Scholar
  37. 37.
    Roy P, Marshall JA, French TJ (1990) Structure of bluetongue virus genome and its encoded proteins. Curr Top Microbiol Immunol 162: 43–87PubMedGoogle Scholar
  38. 38.
    Stuart DI, Gouet P, Grimes J, Malby R, Diprose J, Zientara S, Burroughs JN, Mertens PPC (1998) Structural studies of orbivirus particles. In: Mellor PS, Baylis M, Hamblin C, Calisher CH, Mertens PPC (eds) African horse sickness. Springer, Wien New York, pp 235–250 (Arch Virol [Suppl] 14 )Google Scholar
  39. 39.
    Urakawa T, French TJ, Adachi Y, Fukusho A, LeBlois H, Flamand M, Mertens PPC, Roy P (1994) Synthesis of recombinant baculoviruses expressing the outer capsid protein VP2 of five BTV serotypes and the induction of neutralising antibodies to homologous and heterologous BTV serotypes. Virus Res 31: 149–161PubMedCrossRefGoogle Scholar
  40. 40.
    Verwoerd DW, Els HJ, De Villiers E-M, Huismans H (1972) Structure of the blue-tongue virus capsid. J Virol 110: 783–794Google Scholar
  41. 41.
    Yang YY, Li JK (1992) Complete genomic sequences of the VP5 protein gene of bluetongue virus serotype 11 and 17. Virus Res 23: 163–171PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag/Wien 1998

Authors and Affiliations

  • P. Roy
    • 1
    • 3
  • G. Sutton
    • 2
  1. 1.Department of BiochemistryUniversity of OxfordOxfordUK
  2. 2.NERC Institute of Virology and Environmental MicrobiologyOxfordUK
  3. 3.Department of BiochemistryUniversity of OxfordOxfordUK

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