1887

Abstract

Vaccination of pigs against (CSFV) by using live-virus vaccines induces early protection before detectable humoral immune responses. Immunological analyses indicate that this is associated with T-cell activation, underlining the importance of targeting cytotoxic T-lymphocyte (CTL) responses for vaccine improvement. Antigen-presenting cells (APCs) transfected with mRNA encoding structural protein E2 or non-structural viral proteins NS3–NS4A were used to identify viral genes encoding CTL epitopes. Monocyte-derived dendritic cells (DCs) and fibrocytes served as the APCs. translation of the mRNA and microscopic analysis of transfected cells demonstrated that E2 and NS3–NS4A could be identified. APCs transfected with either of the mRNA molecules restimulated CSFV-specific T cells to produce gamma interferon and specific cytotoxic activity against CSFV-infected target cells. The presence of CTL epitopes on E2 was confirmed by using d/d-haplotype MAX cells expressing E2 constitutively as target cells in d/d-haplotype CTL assays. A potent CTL activity against E2 was detected early (1–3 weeks) after CSFV challenge. This work corroborates the existence of CTL epitopes within the non-structural protein domain NS3–NS4A of CSFV. Furthermore, epitopes on the E2 protein can also now be classified as targets for CTLs, having important implications for vaccine design, especially subunit vaccines. As for the use of mRNA-transfected APCs, this represents a simple and efficient method to identify viral genes encoding CTL epitopes in outbred populations.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.80907-0
2005-09-01
2019-11-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/86/9/vir862525.html?itemId=/content/journal/jgv/10.1099/vir.0.80907-0&mimeType=html&fmt=ahah

References

  1. Alvarez, B., Sánchez, C., Bullido, R., Marina, A., Lunney, J., Alonso, F., Ezquerra, A. & Domínguez, J. ( 2000; ). A porcine cell surface receptor identified by monoclonal antibodies to SWC3 is a member of the signal regulatory protein family and associates with protein-tyrosine phosphatase SHP-1. Tissue Antigens 55, 342–351.[CrossRef]
    [Google Scholar]
  2. Armengol, E., Wiesmüller, K.-H., Wienhold, D., Büttner, M., Pfaff, E., Jung, G. & Saalmüller, A. ( 2002; ). Identification of T-cell epitopes in the structural and non-structural proteins of classical swine fever virus. J Gen Virol 83, 551–560.
    [Google Scholar]
  3. Balmelli, C., Ruggli, N., McCullough, K. & Summerfield, A. ( 2005; ). Fibrocytes are potent stimulators of anti-virus cytotoxic T cells. J Leukoc Biol 77, 923–933.[CrossRef]
    [Google Scholar]
  4. Bungener, L., Huckriede, A., Wilschut, J. & Daemen, T. ( 2002; ). Delivery of protein antigens to the immune system by fusion-active virosomes: a comparison with liposomes and ISCOMs. Biosci Rep 22, 323–338.[CrossRef]
    [Google Scholar]
  5. Carralot, J.-P., Probst, J., Hoerr, I., Scheel, B., Teufel, R., Jung, G., Rammensee, H.-G. & Pascolo, S. ( 2004; ). Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines. Cell Mol Life Sci 61, 2418–2424.
    [Google Scholar]
  6. Carrasco, C. P., Rigden, R. C., Schaffner, R. & 7 other authors ( 2001; ). Porcine dendritic cells generated in vitro: morphological, phenotypic and functional properties. Immunology 104, 175–184.[CrossRef]
    [Google Scholar]
  7. Ceppi, M., Ruggli, N., Tache, V., Gerber, H., McCullough, K. C. & Summerfield, A. ( 2005; ). Double-stranded secondary structures on mRNA induce type I interferon (IFN α/β) production and maturation of mRNA-transfected monocyte-derived dendritic cells. J Gene Med 7, 452–465.[CrossRef]
    [Google Scholar]
  8. Chikh, G. & Schutze-Redelmeier, M.-P. ( 2002; ). Liposomal delivery of CTL epitopes to dendritic cells. Biosci Rep 22, 339–353.[CrossRef]
    [Google Scholar]
  9. Dahle, J. & Liess, B. ( 1995; ). Assessment of safety and protective value of a cell culture modified strain “C” vaccine of hog cholera/classical swine fever virus. Berl Munch Tierarztl Wochenschr 108, 20–25.
    [Google Scholar]
  10. de Bruin, T. G. M., van Rooij, E. M. A., de Visser, Y. E., Voermans, J. J. M., Samsom, J. N., Kimman, T. G. & Bianchi, A. T. J. ( 2000; ). Discrimination of different subsets of cytolytic cells in pseudorabies virus-immune and naive pigs. J Gen Virol 81, 1529–1537.
    [Google Scholar]
  11. Dewulf, J., Laevens, H., Koenen, F., Mintiens, K. & de Kruif, A. ( 2004; ). Efficacy of E2-sub-unit marker and C-strain vaccines in reducing horizontal transmission of classical swine fever virus in weaner pigs. Prev Vet Med 65, 121–133.[CrossRef]
    [Google Scholar]
  12. Greiser-Wilke, I., Moennig, V., Coulibaly, C. O. Z., Dahle, J., Leder, L. & Liess, B. ( 1990; ). Identification of conserved epitopes on a hog cholera virus protein. Arch Virol 111, 213–225.[CrossRef]
    [Google Scholar]
  13. Greiser-Wilke, I., Dittmar, K. E., Liess, B. & Moennig, V. ( 1992; ). Heterogeneous expression of the non-structural protein p80/p125 in cells infected with different pestiviruses. J Gen Virol 73, 47–52.[CrossRef]
    [Google Scholar]
  14. Hoerr, I., Obst, R., Rammensee, H.-G. & Jung, G. ( 2000; ). In vivo application of RNA leads to induction of specific cytotoxic T lymphocytes and antibodies. Eur J Immunol 30, 1–7.[CrossRef]
    [Google Scholar]
  15. Knoetig, S. M., Summerfield, A., Spagnuolo-Weaver, M. & McCullough, K. C. ( 1999; ). Immunopathogenesis of classical swine fever: role of monocytic cells. Immunology 97, 359–366.[CrossRef]
    [Google Scholar]
  16. Koziel, M. J., Dudley, D., Afdhal, N., Choo, Q.-L., Houghton, M., Ralston, R. & Walker, B. D. ( 1993; ). Hepatitis C virus (HCV)-specific cytotoxic T lymphocytes recognize epitopes in the core and envelope proteins of HCV. J Virol 67, 7522–7532.
    [Google Scholar]
  17. Maurer, R., Stettler, P., Ruggli, N., Hofmann, M. A. & Tratschin, J. D. ( 2005; ). Oronasal vaccination with classical swine fever virus (CSFV) replicon particles with either partial or complete deletion of the E2 gene induces partial protection against lethal challenge with highly virulent CSFV. Vaccine 23, 3318–3328.[CrossRef]
    [Google Scholar]
  18. McCullough, K. C., Schaffner, R., Fraefel, W. & Kihm, U. ( 1993; ). The relative density of CD44-positive porcine monocytic cell populations varies between isolations and upon culture and influences susceptibility to infection by African swine fever virus. Immunol Lett 37, 83–90.[CrossRef]
    [Google Scholar]
  19. Meyers, G. & Thiel, H.-J. ( 1996; ). Molecular characterization of pestiviruses. Adv Virus Res 47, 53–118.
    [Google Scholar]
  20. Meyers, G., Rümenapf, T. & Thiel, H.-J. ( 1989; ). Molecular cloning and nucleotide sequence of the genome of hog cholera virus. Virology 171, 555–567.[CrossRef]
    [Google Scholar]
  21. Morón, G., Dadaglio, G. & Leclerc, C. ( 2004; ). New tools for antigen delivery to the MHC class I pathway. Trends Immunol 25, 92–97.[CrossRef]
    [Google Scholar]
  22. Pauly, T., Elbers, K., König, M., Lengsfeld, T., Saalmüller, A. & Thiel, H.-J. ( 1995; ). Classical swine fever virus-specific cytotoxic T lymphocytes and identification of a T cell epitope. J Gen Virol 76, 3039–3049.[CrossRef]
    [Google Scholar]
  23. Peeters, B., de Wind, N., Broer, R., Gielkens, A. & Moormann, R. ( 1992; ). Glycoprotein H of pseudorabies virus is essential for entry and cell-to-cell spread of the virus. J Virol 66, 3888–3892.
    [Google Scholar]
  24. Ponsaerts, P., Van Tendeloo, V. F. I. & Berneman, Z. N. ( 2003; ). Cancer immunotherapy using RNA-loaded dendritic cells. Clin Exp Immunol 134, 378–384.[CrossRef]
    [Google Scholar]
  25. Racanelli, V., Behrens, S.-E., Aliberti, J. & Rehermann, B. ( 2004; ). Dendritic cells transfected with cytopathic self-replicating RNA induce crosspriming of CD8+ T cells and antiviral immunity. Immunity 20, 47–58.[CrossRef]
    [Google Scholar]
  26. Roehrig, J. T. ( 2003; ). Antigenic structure of flavivirus proteins. Adv Virus Res 59, 141–175.
    [Google Scholar]
  27. Ruggli, N., Tratschin, J. D., Mittelholzer, C. & Hofmann, M. A. ( 1996; ). Nucleotide sequence of classical swine fever virus strain Alfort/187 and transcription of infectious RNA from stably cloned full-length cDNA. J Virol 70, 3478–3487.
    [Google Scholar]
  28. Sarobe, P., Huarte, E., Lasarte, J. J., López-Díaz de Cerio, A., García, N., Borrás-Cuesta, F. & Prieto, J. ( 2001; ). Characterization of an immunologically conserved epitope from hepatitis C virus E2 glycoprotein recognized by HLA-A2 restricted cytotoxic T lymphocytes. J Hepatol 34, 321–329.[CrossRef]
    [Google Scholar]
  29. Schubert, U., Antón, L. C., Gibbs, J., Norbury, C. C., Yewdell, J. W. & Bennink, J. R. ( 2000; ). Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature 404, 770–774.[CrossRef]
    [Google Scholar]
  30. Strobel, I., Berchtold, S., Götze, A., Schulze, U., Schuler, G. & Steinkasserer, A. ( 2000; ). Human dendritic cells transfected with either RNA or DNA encoding influenza matrix protein M1 differ in their ability to stimulate cytotoxic T lymphocytes. Gene Ther 7, 2028–2035.[CrossRef]
    [Google Scholar]
  31. Suradhat, S., Intrakamhaeng, M. & Damrongwatanapokin, S. ( 2001; ). The correlation of virus-specific interferon-gamma production and protection against classical swine fever virus infection. Vet Immunol Immunopathol 83, 177–189.[CrossRef]
    [Google Scholar]
  32. Terpstra, C. & Wensvoort, G. ( 1988; ). The protective value of vaccine-induced neutralising antibody titres in swine fever. Vet Microbiol 16, 123–128.[CrossRef]
    [Google Scholar]
  33. Terpstra, C., Woortmeyer, R. & Barteling, S. J. ( 1990; ). Development and properties of a cell culture produced vaccine for hog cholera based on the Chinese strain. Dtsch Tierarztl Wochenschr 97, 77–79.
    [Google Scholar]
  34. Thornburg, C., Boczkowski, D., Gilboa, E. & Nair, S. K. ( 2000; ). Induction of cytotoxic T lymphocytes with dendritic cells transfected with human papillomavirus E6 and E7 RNA: implications for cervical cancer immunotherapy. J Immunother 23, 412–418.[CrossRef]
    [Google Scholar]
  35. Tuyaerts, S., Michiels, A., Corthals, J., Bonehill, A., Heirman, C., De Greef, C., Noppe, S. M. & Thielemans, K. ( 2003; ). Induction of influenza matrix protein 1 and MelanA-specific T lymphocytes in vitro using mRNA-electroporated dendritic cells. Cancer Gene Ther 10, 696–706.[CrossRef]
    [Google Scholar]
  36. Ueno, H., Tcherepanova, I., Reygrobellet, O., Laughner, E., Ventura, C., Palucka, A. K. & Banchereau, J. ( 2004; ). Dendritic cell subsets generated from CD34+ hematopoietic progenitors can be transfected with mRNA and induce antigen-specific cytotoxic T cell responses. J Immunol Methods 285, 171–180.[CrossRef]
    [Google Scholar]
  37. van Gennip, H. G. P., Bouma, A., van Rijn, P. A., Widjojoatmodjo, M. N. & Moormann, R. J. M. ( 2002; ). Experimental non-transmissible marker vaccines for classical swine fever (CSF) by trans-complementation of Erns or E2 of CSFV. Vaccine 20, 1544–1556.[CrossRef]
    [Google Scholar]
  38. van Oirschot, J. T. ( 2003; ). Vaccinology of classical swine fever: from lab to field. Vet Microbiol 96, 367–384.[CrossRef]
    [Google Scholar]
  39. Van Tendeloo, V. F. I., Ponsaerts, P., Lardon, F., Nijs, G., Lenjou, M., Van Broekhoven, C., Van Bockstaele, D. R. & Berneman, Z. N. ( 2001; ). Highly efficient gene delivery by mRNA electroporation in human hematopoietic cells: superiority to lipofection and passive pulsing of mRNA and to electroporation of plasmid cDNA for tumor antigen loading of dendritic cells. Blood 98, 49–56.[CrossRef]
    [Google Scholar]
  40. Weissman, D., Ni, H., Scales, D. & 7 other authors ( 2000; ). HIV gag mRNA transfection of dendritic cells (DC) delivers encoded antigen to MHC class I and II molecules, causes DC maturation, and induces a potent human in vitro primary immune response. J Immunol 165, 4710–4717.[CrossRef]
    [Google Scholar]
  41. Wensvoort, G., Terpstra, C., De Kluijver, E. P., Kragten, C. & Warnaar, J. C. ( 1989; ). Antigenic differentiation of pestivirus strains with monoclonal antibodies against hog cholera virus. Vet Microbiol 21, 9–20.[CrossRef]
    [Google Scholar]
  42. Widjojoatmodjo, M. N., van Gennip, H. G. P., Bouma, A., van Rijn, P. A. & Moormann, R. J. M. ( 2000; ). Classical swine fever virus Erns deletion mutants: trans-complementation and potential use as nontransmissible, modified, live-attenuated marker vaccines. J Virol 74, 2973–2980.[CrossRef]
    [Google Scholar]
  43. Yewdell, J. W., Schubert, U. & Bennink, J. R. ( 2001; ). At the crossroads of cell biology and immunology: DRiPs and other sources of peptide ligands for MHC class I molecules. J Cell Sci 114, 845–851.
    [Google Scholar]
  44. Zarei, S., Arrighi, J.-F., Ongaro, G., Calzascia, T., Haller, O., Frossard, C., Piguet, V., Walker, P. R. & Hauser, C. ( 2003; ). Efficient induction of CD8 T-associated immune protection by vaccination with mRNA transfected dendritic cells. J Invest Dermatol 121, 745–750.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.80907-0
Loading
/content/journal/jgv/10.1099/vir.0.80907-0
Loading

Data & Media loading...

Most Cited This Month

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