1887

Abstract

We have previously developed an antigen-delivery system based on hybrid recombinant porcine parvovirus-like particles (PPV-VLPs) formed by the self-assembly of the VP2 protein of PPV carrying a foreign epitope at its N terminus. In this study, different constructs were made containing a CD8 T-cell epitope of chicken ovalbumin (OVA) to analyse the influence of the sequence inserted into VP2 on the correct processing of VLPs by antigen-presenting cells. We analysed the presentation of the OVA epitope inserted without flanking sequences or with either different natural flanking sequences or with the natural flanking sequences of a CD8 T-cell epitope from the lymphocytic choriomeningitis virus nucleoprotein, and as a dimer with or without linker sequences. All constructs were studied in terms of level of expression, assembly of VLPs and ability to deliver the inserted epitope into the MHC I pathway. The presentation of the OVA epitope was considerably improved by insertion of short natural flanking sequences, which indicated the relevance of the flanking sequences on the processing of PPV-VLPs. Only PPV-VLPs carrying two copies of the OVA epitope linked by two glycines were able to be properly processed, suggesting that the introduction of flexible residues between the two consecutive OVA epitopes may be necessary for the correct presentation of these dimers by PPV-VLPs. These results provide information to improve the insertion of epitopes into PPV-VLPs to facilitate their processing and presentation by MHC class I molecules.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.19525-0
2004-03-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/85/3/vir850563.html?itemId=/content/journal/jgv/10.1099/vir.0.19525-0&mimeType=html&fmt=ahah

References

  1. Altschul S. F., Madden T. L., Schaffer A. A., Zhang J., Zhang Z., Miller W., Lipman D. J. 1997; Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402
    [Google Scholar]
  2. Casal J. I. 1999; Use of parvovirus-like particles for vaccination and induction of multiple immune responses. Biotechnol Appl Biochem 29:141–150
    [Google Scholar]
  3. Casal J. I. 2001; Use of the baculovirus expression system for the generation of virus-like particles. Biotechnol Genet Eng Rev 18:73–87
    [Google Scholar]
  4. Casal J. I., Cortés E., López de Turiso J. A., Vela C. 1992; Production of porcine and canine parvovirus-like particles using recombinant baculovirus. In Baculovirus and Recombinant Protein Production Processes pp  76–91 Edited by Vlak J. M., Schlaeger E. S., Bernard A. Basel: Editiones Roches;
    [Google Scholar]
  5. Casal J. I., Rueda P., Hurtado A. 1999; Parvovirus-like particles as vaccine vectors. Methods 19:174–186
    [Google Scholar]
  6. Cascio P., Hilton C., Kisselev A. F., Rock K. L., Goldberg A. L. 2001; 26S proteasomes and immunoproteasomes produce mainly N-extended versions of an antigenic peptide. EMBO J 20:2357–2366
    [Google Scholar]
  7. Cortes E., San Martin C., Langeveld J., Meloen R., Dalsgaard K., Vela C., Casal I. 1993; Topographical analysis of canine parvovirus virions and recombinant VP2 capsids. J Gen Virol 74:2005–2010
    [Google Scholar]
  8. Cotmore S. F., Tattersall P. 1987; The autonomously replicating parvoviruses of vertebrates. Adv Virus Res 33:91–174
    [Google Scholar]
  9. Del-Val M., Lopez D. 2002; Multiple proteases process viral antigens for presentation by MHC class I molecules to CD8+ T lymphocytes. Mol Immunol 39:235–247
    [Google Scholar]
  10. Del Val M., Schlicht H. J., Ruppert T., Reddehase M. J., Koszinowski U. H. 1991; Efficient processing of an antigenic sequence for presentation by MHC class I molecules depends on its neighboring residues in the protein. Cell 66:1145–1153
    [Google Scholar]
  11. Fayolle C., Osickova A., Osicka R., Henry T., Rojas M. J., Saron M. F., Sebo P., Leclerc C. 2001; Delivery of multiple epitopes by recombinant detoxified adenylate cyclase of Bordetella pertussis induces protective antiviral immunity. J Virol 75:7330–7338
    [Google Scholar]
  12. Gilbert S. C., Plebanski M., Harris S. J., Allsopp C. E., Thomas R., Layton G. T., Hill A. V. 1997; A protein particle vaccine containing multiple malaria epitopes. Nat Biotechnol 15:1280–1284
    [Google Scholar]
  13. Hurtado A., Rueda P., Nowicky J., Sarraseca J., Casal J. I. 1996; Identification of domains in canine parvovirus VP2 essential for the assembly of virus-like particles. J Virol 70:5422–5429
    [Google Scholar]
  14. Jameson S. C., Bevan M. J. 1992; Dissection of major histocompatibility complex (MHC) and T cell receptor contact residues in a Kb-restricted ovalbumin peptide and an assessment of the predictive power of MHC-binding motifs. Eur J Immunol 22:2663–2667
    [Google Scholar]
  15. Karttunen J., Sanderson S., Shastri N. 1992; Detection of rare antigen-presenting cells by the lacZ T-cell activation assay suggests an expression cloning strategy for T-cell antigens. Proc Natl Acad Sci U S A 89:6020–6024
    [Google Scholar]
  16. Lo-Man R., Rueda P., Sedlik C., Deriaud E., Casal I., Leclerc C. 1998; A recombinant virus-like particle system derived from parvovirus as an efficient antigen carrier to elicit a polarized Th1 immune response without adjuvant. Eur J Immunol 28:1401–1407
    [Google Scholar]
  17. Martinez C., Dalsgaard K., Lopez de Turiso J. A., Cortes E., Vela C., Casal J. I. 1992; Production of porcine parvovirus empty capsids with high immunogenic activity. Vaccine 10:684–690
    [Google Scholar]
  18. Matsuura Y., Posee R. D., Overton H. L., Bishop D. H. L. 1987; Baculovirus expression vectors: the requirements for high level expression of proteins including glycoproteins. J Gen Virol 68:1233–1250
    [Google Scholar]
  19. Mo X. Y., Cascio P., Lemerise K., Goldberg A. L., Rock K. 1999; Distinct proteolytic processes generate the C and N termini of MHC class I-binding peptides. J Immunol 163:5851–5859
    [Google Scholar]
  20. Moore M. W., Carbone F. R., Bevan M. J. 1988; Introduction of soluble protein into the class I pathway of antigen processing and presentation. Cell 54:777–785
    [Google Scholar]
  21. Morón G., Rueda P., Casal I., Leclerc C. 2002; CD8 α 2 CD11b+ dendritic cells present exogenous virus-like particles to CD8+ T cells and subsequently express CD8 α and CD205 molecules. J Exp Med 195:1233–1245
    [Google Scholar]
  22. Morón G., Rueda P., Sedlik C., Leclerc C. 2003; In vivo, dendritic cells can cross-present virus-like particles using an endosome-to-cytosol pathway. J Immunol 171:2242–2250
    [Google Scholar]
  23. Neisig A., Roelse J., Sijts A., Ossendorp F., Feltkamp M., Kast M., Melief C., Neefjes J. 1995; Major differences in transporter associated with antigen presentation (TAP)-dependent translocation of MHC class I-presentable peptides and the effect of flanking sequences. J Immunol 154:1273–1279
    [Google Scholar]
  24. Paradiso P. R. 1981; Infectious process of the parvovirus H-1: correlation of protein content, particle density, and viral infectivity. J Virol 39:800–807
    [Google Scholar]
  25. Paradiso P. R., Rhode S. L. III, Singer I. I. 1982; Canine parvovirus: a biochemical and ultrastructural characterization. J Gen Virol 62:113–125
    [Google Scholar]
  26. Ranz A. I., Manclus J. J., Diaz-Aroca E., Casal J. I. 1989; Porcine parvovirus: DNA sequence and genome organization. J Gen Virol 70:2541–2553
    [Google Scholar]
  27. Rotzschke O., Falk K., Stevanovic S., Jung G., Walden P., Rammensee H. G. 1991; Exact prediction of a natural T cell epitope. Eur J Immunol 21:2891–2894
    [Google Scholar]
  28. Rueda P., Martinez-Torrecuadrada J. L., Sarraseca J., Sedlik C., Del Barrio M., Hurtado A., Leclerc C., Casal J. I. 1999; Engineering parvovirus-like particles for the induction of B-cell, CD4+ and CTL responses. Vaccine 18:325–332
    [Google Scholar]
  29. Rueda P., Fominaya J., Langeveld J. P., Bruschke C., Vela C., Casal J. I. 2001; Effect of different baculovirus inactivation procedures on the integrity and immunogenicity of porcine parvovirus-like particles. Vaccine 19:726–734
    [Google Scholar]
  30. Sedlik C., Sarraseca J., Rueda P., Leclerc C., Casal I. 1995; Immunogenicity of poliovirus B and T cell epitopes presented by hybrid porcine parvovirus particles. J Gen Virol 76:2361–2368
    [Google Scholar]
  31. Sedlik C., Saron M., Sarraseca J., Casal I., Leclerc C. 1997; Recombinant parvovirus-like particles as an antigen carrier: a novel nonreplicative exogenous antigen to elicit protective antiviral cytotoxic T cells. Proc Natl Acad Sci U S A 94:7503–7508
    [Google Scholar]
  32. Sedlik C., Dridi A., Deriaud E., Saron M. F., Rueda P., Sarraseca J., Casal J. I., Leclerc C. 1999; Intranasal delivery of recombinant parvovirus-like particles elicits cytotoxic T-cell and neutralizing antibody responses. J Virol 73:2739–2744
    [Google Scholar]
  33. Sedlik C., Dadaglio G., Saron M. F., Deriaud E., Rojas M., Casal S. I., Leclerc C. 2000; In vivo induction of a high-avidity, high-frequency cytotoxic T-lymphocyte response is associated with antiviral protective immunity. J Virol 74:5769–5775
    [Google Scholar]
  34. Taylor K. M., Lin T., Porta C., Mosser A. G., Giesing H. A., Lomonossoff G. P., Johnson J. E. 2000; Influence of three-dimensional structure on the immunogenicity of a peptide expressed on the surface of a plant virus. J Mol Recognit 13:71–82
    [Google Scholar]
  35. Thomson S. A., Khanna R., Gardner J., Burrows S. R., Coupar B., Moss D. J., Suhrbier A. 1995; Minimal epitopes expressed in a recombinant polyepitope protein are processed and presented to CD8+ cytotoxic T cells: implications for vaccine design. Proc Natl Acad Sci U S A 92:5845–5849
    [Google Scholar]
  36. Tsao J., Chapman M. S., Agbandje M. 8 other authors 1991; The three-dimensional structure of canine parvovirus and its functional implications. Science 251:1456–1464
    [Google Scholar]
  37. Vanhoof G., Goossens F., De Meester I., Hendriks D., Scharp S. 1995; Proline motifs in peptides and their biological processing. FASEB J 9:736–744
    [Google Scholar]
  38. Van Pel A., Van der Bruggen P., Coulie P. G., Brichard V. G., Lethe B., Van den Eynde B., Uyttenhove C., Renauld J. C., Boon T. 1995; Genes coding for tumor antigens recognized by cytolytic T lymphocytes. Immunol Rev 145:229–250
    [Google Scholar]
  39. Woodberry T., Gardner J., Mateo L. 9 other authors; 1999; Immunogenicity of a human immunodeficiency virus (HIV) polytope vaccine containing multiple HLA A2 HIV CD8+ cytotoxic T-cell epitopes. J Virol 73:5320–5325
    [Google Scholar]
  40. Yaron A., Naider F. 1993; Proline-dependent structural and biological properties of peptides and proteins. Crit Rev Biochem Mol Biol 28:31–81
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.19525-0
Loading
/content/journal/jgv/10.1099/vir.0.19525-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error