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Phage display of epitopes from HIV-1 elicits strong cytolytic responses in vitroand in vivo

  • John Guardiola
  • Piergiuseppe De Berardinis
  • Rossella Sartorius
  • Cristina Fanutti
  • Perham N. Richard
  • Giovanna Del Pozzo
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 495)

Abstract

Vaccines based on synthetic peptides representing epitopes recognized by T-helper or cytolytic T-cells have been widely investigated as the basis for effective vaccines. However, their efficacy suffers from a number of important limitations. First, they are poor immunogens and exhibit short life-spans both in serum and within the cell (1). Secondly, the amount of peptide required to bind a threshold number of MHC class II molecules on the surface of an APC is reportedly higher than the minimal amount needed to bind to class II MHC molecules in the intracellular compartment in which the processing of the corresponding parent antigen takes place after internalization (2). Soluble antigens carrying CTL epitopes not only have the same drawbacks, but normally are unable to enter the appropriate intracellular compartment to undergo processing and presentation on class I MHC molecules (3). Thus, delivery systems based on immune-stimulating complexes, liposomes and synthetic lipopeptides have been designed in attempts to circumvent these limitations (1).

Keywords

Phage Display Filamentous Bacteriophage Bacteriophage Virion Major Coat Protein Hybrid Bacteriophage 
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.
    Bona, C. A., S. Casares, T. D. Brumeanu. 1998. Towards development of T-cell vaccines.Immunol Today.19: 126–33PubMedGoogle Scholar
  2. 2.
    Demotz, S., H. M. Grey, A. Sette. 1990. The minimal number of class II MHC-antigen complexes needed for T cell activation.Science.249: 1028–30PubMedCrossRefGoogle Scholar
  3. 3.
    Bot, A., S. Bot, S. Antohi, K. Karjalainen, C. Bona. 1996. Kinetics of generation and persistence on membrane class II molecules of a viral peptide expressed on foreign and self proteins.J Immunol.157: 3436–42PubMedGoogle Scholar
  4. 4.
    Greenwood, J., A. E. Willis, R. N. Perham. 1991. Multiple display of foreign peptides on a filamentous bacteriophage. Peptides from Plasmodium falciparum circumsporozoite protein as antigens.JMoI Biol.220: 821–7CrossRefGoogle Scholar
  5. 5.
    Minenkova, O. O., A. A. Ilyichev, G. P. Kishchenko, V. A. Petrenko. 1993. Design of specific immunogens using filamentous phage as the carrier.Gene.128: 85–8PubMedCrossRefGoogle Scholar
  6. 6.
    Malik, P., R. N. Perham. 1996. New vectors for peptide display on the surface of filamentous bacteriophage.Gene.171: 49–51PubMedCrossRefGoogle Scholar
  7. 7.
    Malik, P., R. N. Perham. 1997. Simultaneous display of different peptides on the surface of filamentous bacteriophage.Nucleic Acids Res.25: 915–6PubMedCrossRefGoogle Scholar
  8. 8.
    di Marzo Veronese, F., A. E. Willis, C. Boyer-Thompson, E. Appella, R. N. Perham. 1994. Structural mimicry and enhanced immunogenicity of peptide epitopes displayed on-filamentous bacteriophage. The V3 loop of HIV-1 gp120.JMo1 Biol.243: 167–72CrossRefGoogle Scholar
  9. 9.
    Jelinek, R., T. D. Terry, J. J. Gesell, P. Malik, R. N. Perham, S. J. Opella. 1997. NMR structure of the principal neutralizing determinant of HIV-1 displayed in filamentous bacteriophage coat protein.J Mol Biol.266: 649–55PubMedCrossRefGoogle Scholar
  10. 10.
    De Berardinis, P., L. D’Apice, A. Prisco, M. N. Ombra, P. Barba, G. Del Pozzo, S. Petukhov, P. Malik, R. N. Perham, J. Guardiola. 1999. Recognition of HIV-derived B and T cell epitopes displayed on filamentous phages.Vaccine.17: 1434–41PubMedCrossRefGoogle Scholar
  11. 11.
    Ogg, G. S., X. Jin, S. Bonhoeffer, P. R. Dunbar, M. A. Nowak, S. Monard, J. P. Segal, Y. Cao, S. L. Rowland-Jones, V. Cerundolo, A. Hurley, M. Markowitz, D. D. Ho, D. F. Nixon, A. J. McMichael. 1998. Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA.Science.279: 2103–6PubMedCrossRefGoogle Scholar
  12. 12.
    Stuhler, G., S. F. Schlossman. 1997. Antigen organization regulates cluster formation and induction of cytotoxic T lymphocytes by helper T cell subsets.Proc Natl Acad Sci USA.94: 622–7PubMedCrossRefGoogle Scholar
  13. 13.
    Ossendorp, F., E. Mengede, M. Camps, R. Filius, C. J. Melief. 1998. Specific T helper cell requirement for optimal induction of cytotoxic T lymphocytes against major histocompatibility complex class II negative tumors.JExp Med.187: 693–702CrossRefGoogle Scholar
  14. 14.
    Keene, J. A., J. Forman. 1982. Helper activity is required for the in vivo generation of cytotoxic T lymphocytes.J Exp Med.155: 768–82PubMedCrossRefGoogle Scholar
  15. 15.
    Manca, F., P. De Berardinis, D. Fenoglio, M. N. Ombra, G. Li Pira, D. Saverino, M. Autiero, L. Lozzi, L. Bracci, J. Guardiola. 1996. Antigenicity of HIV-derived T helper determinants in the context of carrier recombinant proteins: effect on T helper cell repertoire selection.Eur J Immunol.26: 2461–9PubMedCrossRefGoogle Scholar
  16. 16.
    Menendez-Arias, L., A. Mas, E. Domingo. 1998. Cytotoxic T-lymphocyte responses to HIV-I reverse transcriptase (review).Viral Immunol. 11: 167–81PubMedCrossRefGoogle Scholar
  17. 17.
    Pascolo, S., N. Bervas, J. M. Ure, A. G. Smith, F. A. Lemonnier, B. Perarnau. 1997. FILAA2.1-restricted education and cytolytic activity of CD8(+) T lymphocytes from beta2 microglobulin (beta2m) HLA-A2.1 monochain transgenic H-2Db beta2m double knockout mice.J Exp Med.185: 2043–51PubMedCrossRefGoogle Scholar
  18. 18.
    Vitiello, A., D. Marchesini, J. Furze, L. A. Sherman, R. W. Chesnut. 1991. Analysis of the HLA-restricted influenza-specific cytotoxic T lymphocyte response in transgenic mice carrying a chimeric human-mouse class I major histocompatibility complex.J Exp Med.173: 1007–15PubMedCrossRefGoogle Scholar
  19. 19.
    Ren, J., R. Esnouf, E. Garman, D. Somers, C. Ross, I. Kirby, J. Keeling, G. Darby, Y. Jones, D. Stuart, et al. 1995. High resolution structures of HIV-1 RT from four RT-inhibitor complexes.Nat Struct Biol.2: 293–302PubMedCrossRefGoogle Scholar
  20. 20.
    Grimison, B., J. Laurence. 1995. Immunodominant epitope regions of HIV-1 reverse transcriptase: correlations with HIV-1+ serum IgG inhibitory to polymerase activity and with disease progression.J Acquir Immune Defic Syndr Hum Retrovirol.9: 58–68PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • John Guardiola
    • 1
  • Piergiuseppe De Berardinis
    • 2
  • Rossella Sartorius
    • 2
  • Cristina Fanutti
    • 3
  • Perham N. Richard
    • 3
  • Giovanna Del Pozzo
    • 1
  1. 1.International Institute of Genetics and BiophysicsCNRNaplesItaly
  2. 2.Institute of Protein Biochemistry EnzymologyCNRNaplesItaly
  3. 3.Department of BiochemistryUniversity of CambridgeUK

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