Skip to main content
SpringerLink
Log in

Retrovirus and Retrotransposon Particles as Antigen Presentation and Delivery Systems

  • Chapter
Vaccine Design

Part of the book series: Pharmaceutical Biotechnology ((PBIO,volume 6))

Abstract

The development of technologies to produce recombinant proteins for use as vaccines has made substantial advances during the past decade. In particular, a number of expression systems have been designed to increase the immunogenicity of proteins and peptides by presenting them as polyvalent, paniculate structures. Examples of such carrier systems include both the core and surface proteins of hepatitis B virus and poliovirus which have been used to present a variety of immunogens in a particulate form; these include epitopes derived from foot-and-mouth disease virus (Clarke et al., 1987), human immunodeficiency virus (HIV-1) (Michel et al., 1988), and human papillomavirus (Jenkins et al., 1991). In addition, synthetic systems such as immunostimulating complexes (ISCOMs) (Morein et al., 1987; see Chapter 23) and liposomes (Harding et al., 1991; see Chapter 13) have been used to induce both cellular and humoral responses to a range of proteins. Both of these systems result in multiple copies of the protein being presented to the immune system as part of a relatively large particle.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 74.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adams, S. E., Mellor, J., Gull, K., Sim, R. B., Tuite, M. F., Kingsman, S. M., and Kingsman, A. J., 1987a, The functions and relationships of Ty-VLP proteins in yeast reflect those of mammalian retroviral proteins, Cell 49:111–119.

    Article  PubMed  CAS  Google Scholar 

  • Adams, S. E., Dawson, K. M., Gull, K., Kingsman, S. M., and Kingsman, A. J., 1987b, The expression of hybrid Ty virus-like particles in yeast, Nature 329:68–70.

    Article  PubMed  CAS  Google Scholar 

  • Adams, S. E., Senior, J. M., Kingsman, S. M., and Kingsman, A. J., 1988, Induction of HIV antibodies by Ty:HIV hybrid virus-like particles, in: Technological Advances in Vaccine Development (L. Lasky, ed.) Liss, New York, pp. 117–126.

    Google Scholar 

  • Berman, P. W., Gregory, T. J., Riddle, L., Nakamura, G. R., Champe, M. A., Porter, J. P., Worm, F. M., Herschberg, R. D., Cobb, E. K., and Eichberg, J. W., 1990, Protection of chimpanzees from infection with HIV-1 after vaccination with recombinant glycoprotein gp 120 but not gp 160, Nature 345:622–625.

    Article  PubMed  CAS  Google Scholar 

  • Boeke, J. D., Garfinkel, D. J., Styles, C. A., and Fink, G. R., 1985, Ty elements transpose through an RNA intermediate, Cell 40:491–500.

    Article  PubMed  CAS  Google Scholar 

  • Braddock, M., Chambers, A., Wilson, W., Esnouf, M. P., Adams, S. E., Kingsman, A. J., and Kingsman, S. M., 1989, HIV-1 TAT ‘activates’ presynthesized RNA in the nucleus, Cell 58:269–279.

    Article  PubMed  CAS  Google Scholar 

  • Burns, N. R., Saibil, H. R., White, N. S., Pardon, J. F., Timmins, P. A., Richardson, S. M. H., Richards, B. M., Adams, S. E., Kingsman, S. M., and Kingsman, A. J., 1990a, Symmetry, flexibility and permeability in the structure of yeast retrotransposon virus-like particles, EMBO J. 11:1155–1164.

    Google Scholar 

  • Burns, N. R., Gilmour, J. E. M., Kingsman, S. M., Kingsman, A. J., and Adams, S. E., 1990b, Production and purification of hybrid Ty-VLPs, Methods Mol. Biol. 8:277–285.

    Google Scholar 

  • Cheingsong-Popov, R., Panagiotidi, C., Bowcock, S., Aronstam, A., Wadsworth, J., and Weber, J., 1991, Relation between humoral responses to HIV gag and env proteins at seroconversion and clinical outcome of HIV infection, Br. Med. J. 302:23–26.

    Article  CAS  Google Scholar 

  • Clare, J., and Farabaugh, P., 1985, Nucleotide sequence of a yeast Ty element: Evidence for an unusual mechanism of gene expression, Proc. Natl. Acad. Sci. USA 82:2829–2833.

    Article  PubMed  CAS  Google Scholar 

  • Clarke, B. E., Newton S. E., Carroll, A. R., Francis, M. J., Appleyard, G., Syred, A. D., Highfield, P. E., Rowlands, D. J., and Brown, F., 1987, Improved immunogenicity of a peptide epitope after fusion to hepatitis B core protein, Nature 330:381–384.

    Article  PubMed  CAS  Google Scholar 

  • Deres, K., Schild, H., Weismuller, K. H., Jung, G., and Rammensee, H. G., 1989, In vivo priming of virus-specific cytotoxic T lymphocytes with synthetic lipopeptide vaccine, Nature 342:561–564.

    Article  PubMed  CAS  Google Scholar 

  • Dobson, M. J., Mellor, J., Fulton, A. M., Roberts, N. A., Bowen, B. A., Kingsman, S. M., and Kingsman, A. J., 1984, The identification and high level expression of a protein encoded by the yeast Ty element, EMBO 73: 1115–1119.

    Google Scholar 

  • Eichinger, D. J., and Boeke, J. D., 1988, The DNA intermediate in yeast Ty1 transposition copurifies with virus-like particles: Cell-free Ty1 transposition, Cell 54:955–966.

    Article  PubMed  CAS  Google Scholar 

  • Elder, R. T., Loh, E. Y., and Davis, R. W., 1983, RNA from the yeast transposable element Ty1 has both ends in the direct repeats, a structure similar to retrovirus RNA, Proc. Natl. Acad. Sci. USA 80:2432–2436.

    Article  PubMed  CAS  Google Scholar 

  • Emini, E. A., Scheif, W. A., Nunberg, J. H., Conley, A. J., Eda, Y., Tokiyoshi, S., Putney, S. D., Matsushita, S., Cobb, K. E., Jett, C. M., Eichberg, J. W., and Murthy, K. K., 1992, Prevention of HIV-1 infection in chimpanzees by gpl20 V3 domain-specific monoclonal antibody, Nature 355:728–729.

    Article  PubMed  CAS  Google Scholar 

  • Fulton, A. M., Mellor, J., Dobson, M. J., Chester, J., Warmington, J. R., Indge, K. J., Oliver, S. G., de la Paz, P., Wilson, W., Kingsman, A. J., and Kingsman, S. M., 1985, Variants within the yeast Ty sequence family encode a class of structurally conserved proteins, Nucleic Acids Res. 13:4097–4112.

    Article  PubMed  CAS  Google Scholar 

  • Fulton, A. M., Adams, S. E., Rathjen, P. D., Wilson, W., Kingsman, S. M., and Kingsman, A. J., 1990, The biology and exploitation of the yeast retrotransposon Ty, Adv. Gene Technol. 1:1–20.

    Article  Google Scholar 

  • Gao, X.-M., Zheng, B., Liew, F. Y., Brett, S., and Tite, J., 1991, Priming of influenza virus-specific cytotoxic T lymphocytes in vivo by short synthetic peptides, J. Immunol. 147:3268–3273.

    PubMed  CAS  Google Scholar 

  • Gheyson, D., Jacobs, E., DeForesta, F., Thiriart, C., Francotte, M., Thines, D., and de Wilde, M., 1989, Assembly and release of HIV-1 precursor Pr55gag virus-like particles from recombinant baculovirusinfected cells, Cell 59:103–112.

    Article  Google Scholar 

  • Gilmour, J. E. M., Senior, J. M., Burns, N. R., Esnouf, M. P., Gull, K., Kingsman, S. M., Kingsman, A. J., and Adams, S. E., 1989, A novel method for the purification of HIV-1 p24 protein from hybrid Ty-VLPs, AIDS 3:717–723.

    Article  PubMed  CAS  Google Scholar 

  • Gilmour, J. E. M., Read, S. J., Eglin, R., Ryan, C., Graff, N. R., Stenner, N., Kingsman, S. M., Kingsman, A. J., and Adams, S. E., 1990, Performance characteristics of a novel immunoassay based on hybrid Ty virus-like particles, AIDS 4:967–973.

    Article  PubMed  CAS  Google Scholar 

  • Griffiths, J. C., Berrie, E. L., Holdsworth, L. N., Moore, J. P., Harris, S. J., Senior, J. M., Kingsman, S. M., Kingsman, A. J., and Adams, S. E., 1991, Induction of high-titer neutralizing antibodies using hybrid human immunodeficiency virus V3-Ty virus-like particles in a clinically relevant adjuvant, J. Virol. 65:450–456.

    PubMed  CAS  Google Scholar 

  • Griffiths, J. C., Harris, S. J., Layton, G. T., Berrie, E. L., French, T. J., Burns, N. R., Adams, S. E., and Kingsman, A. J., 1993, Hybrid human immunodeficiency virus Gag particles as an antigen carrier system: Induction of cytotoxic T-cell and humoral responses by a Gag:V3 fusion, J. Virol. 67:3191–3198.

    PubMed  CAS  Google Scholar 

  • Harding, C. V., Collins, D. S., Kanagawa, O., and Unanue, E. R., 1991, Liposome-encapsulated antigens engender lysosomal processing for class II MHC presentation and cytosolic processing for class I presentation, J. Immunol. 147:2860–2863.

    PubMed  CAS  Google Scholar 

  • Harris, S. J., Gearing, A. J. H., Layton, G. T., Adams, S. E., Kingsman, S. M., and Kingsman, A. J., 1992, Enhanced proliferative cellular responses to V3 peptide and gp120 following immunization with V3:Ty virus-like particles, Immunology 77:315–321.

    PubMed  CAS  Google Scholar 

  • Hart, M. K., Weinhold, K. J., Scearce, R. M., Washburn, E. M., Clark, C. A., Palker, T. J., and Haynes, B. F., 1991, Priming of anti-human immunodeficiency virus (HIV) CD8+ cytotoxic T cells in vivo by carrier-free HIV synthetic peptides, Proc. Nail. Acad. Sci. USA 88:9448–9452.

    Article  CAS  Google Scholar 

  • Jenkins, O., Cason, J., Burke, K. L., Lunney, D., Gillen, A., Patel, D., McCance, D. J., and Almond, J. W., 1991, An antigen chimera of poliovirus induces antibodies against human papillomavirus type 16, J. Virol. 64:1201–1206.

    Google Scholar 

  • Kast, W. M., Bronkhorst, A. M., de Waal, L. P., and Melief, C. J. M., 1986, Cooperation between cytotoxic and helper T lymphocytes in protection against lethal Sendai virus infection: Protection by T cells is MHC-restricted, J. Exp. Med. 164:723–738.

    Article  PubMed  CAS  Google Scholar 

  • Kast, W. M., Roux, L., Curren, J., Blom, H. J. J., Voordouw, A. C., Meloen, R. H., Kolakofsky, D., and Melief, C. J. M., 1991, Protection against lethal Sendai virus infection by in vivo priming of virus-specific cytotoxic T lymphocytes with a free synthetic peptide, Proc. Nad. Acad. Sci. USA 88:2283–2287.

    Article  CAS  Google Scholar 

  • Kingsman, A. J., Adams, S. E., Burns, N. R., and Kingsman, S. M., 1991, Retroelement particles as purification, presentation and targeting vehicles, Trends Biotechnol. 9:303–309.

    Article  PubMed  CAS  Google Scholar 

  • Kingsman, S. M., and Kingsman, A. J., 1988, Polyvalent recombinant antigens: A new vaccine strategy, Vaccine 6:304–306.

    Article  PubMed  CAS  Google Scholar 

  • Kitchen, L. W., Barin, F., Sullivan, J. L., McLane, M. F., Brettler, D. B., Levine, P. H., and Essex, M., 1984, Aetiology of AIDS — antibodies to human T-cell leukaemia virus (type III) in haemophiliacs, Nature 312:367–369.

    Article  PubMed  CAS  Google Scholar 

  • Kovacsovics-Bankowski, M., Clark, K., Benacerraf, B., and Rock, K. L., 1993, Efficient major histocompatibility complex class I presentation of exogenous antigen upon phagocytosis by macrophages, Proc. Natl. Acad. Sci. USA 90:4942–4946.

    Article  PubMed  CAS  Google Scholar 

  • Lange, J. M. A., Paul, D. A., Huisman, H. G., de Wolf, F., van den Berg, H., Coutinho, R. A., Danner, S. A., van der Noorda, J., and Goudsmit, J., 1986, Persistent HIV antigenaemia and decline of HIV core antibodies associated with transition to AIDS, Br. Med. J. 293:1459–1463.

    Article  CAS  Google Scholar 

  • Layton, G. T., Harris, S. J., Gearing, A. J. H., Hill-Perkins, M., Cole, J. S., Griffiths, J. C., Burns, N. R., Kingsman, A. J., and Adams, S. E., 1993, Induction of HIV-specific cytotoxic T lymphocytes in vivo with hybrid HIV-1 V3:Ty-virus-like-particles, J. Immunol. 151:1097–1107.

    PubMed  CAS  Google Scholar 

  • Macatonia, S. E., Taylor, P. M., Knight, S. C., and Askonas, B. A., 1989, Primary stimulation by dendritic cells induces antiviral proliferative and cytotoxic T cell responses in vitro, J. Exp. Med. 169:1255–1264.

    Article  PubMed  CAS  Google Scholar 

  • McMichael, A. J., Gotch, F. M., Noble, G. R., and Beare, P. A. S., 1983, Cytotoxic T cell immunity to influenza, N Engl J. Med. 309:13–17.

    Article  PubMed  CAS  Google Scholar 

  • Martin, S. J., Vyakarnum, A., Cheingsong-Popov, R., Callow, D., Jones, K. L., Senior, J. M., Adams, S. E., Kingsman, A. J., Matear, P., Gotch, F. M., McMichael, A. J., Roitt, I. M., and Weber, J. N., 1993, Immunization of human HIV-seronegative volunteers with recombinant p17/p24:Ty virus-like particles elicits HIV-1 p24-specific cellular and humoral immune responses, AIDS 7:1315–1323.

    Article  PubMed  CAS  Google Scholar 

  • Mellor, J., Fulton, A. M., Dobson, M. J., Wilson, W., Kingsman, S. M., and Kingsman, A. J., 1985a, A retrovirus-like strategy for expression of a fusion protein encoded by yeast retrotransposon Ty 1, Nature 313:243–246.

    Article  PubMed  CAS  Google Scholar 

  • Mellor, J., Fulton, A. M., Dobson, M. J., Roberts, N. A., Wilson, W., Kingsman, A. J., and Kingsman, S. M., 1985b, The Ty transposon of Saccharomyces cerevisiae determines the synthesis of at least three proteins, Nucleic Acids Res. 13:6249–6263.

    Article  PubMed  CAS  Google Scholar 

  • Mellor, J., Malim, M. H., Gull, K., Tuite, M. F., McCready, S., Dibbayawan, T., Kingsman, S. M., and Kingsman, A. J., 1985c, Reverse transcriptase activity and Ty RNA are associated with virus-like particles in yeast, Nature 318:583–586.

    Article  PubMed  CAS  Google Scholar 

  • Michel, M.-L., Mancini, M., Sobczack, E., Favier, V., Guetard, D., Bahraqui, E. M., and Tollias, P., 1988, Induction of anti-human immunodeficiency virus (HIV) neutralizing antibodies in rabbits immunized with recombinant HIV-hepatitis B surface antigen particles, Proc. Natl. Acad. Sci. USA 85:7957–7961.

    Article  PubMed  CAS  Google Scholar 

  • Mills, K. H. G., Kitchin, P. A., Mahon, B. P., Barnard, A. L., Adams, S. E., Kingsman, S. M., and Kingsman, A. J., 1990, HIV p24-specific helper Tcell clones from immunized primates recognize highly conserved regions of HIV-1, J. Immunol. 144:1677–1683.

    PubMed  CAS  Google Scholar 

  • Moore, J. P., and Nara, P. L., 1991, The role of the V3 loop of gpl20 in HIV infection, AIDS 5(Suppl. 2):S21–S33.

    Article  PubMed  Google Scholar 

  • Morein, J. P., Lovgren, K., Hogland, S., and Sundquist, B., 1987, The ISCOM: An immunostimulating complex, Immunol. Today 8:333–338.

    Article  CAS  Google Scholar 

  • Moss, B., 1991, Vaccinia virus: A tool for research and vaccine development, Science 252:1662–1667.

    Article  PubMed  CAS  Google Scholar 

  • Nair, S., Zhou, F., Reddy, R., Huang, L., and Rouse, B. T., 1992, Soluble proteins delivered to dendritic cells via pH-sensitive liposomes induce primary cytotoxic T lymphocyte responses in vitro, J. Exp. Med. 175:609–612.

    Article  PubMed  CAS  Google Scholar 

  • Reddy, R., Zhou, F., Nair, S., Huang, L., and Rouse, B. T., 1992, In vivo cytotoxic T lymphocyte induction with soluble proteins administered in liposomes, J. Immunol. 148:1585–1589.

    PubMed  CAS  Google Scholar 

  • Rock, K. L., Rothstein, L., Fleischacker, C., and Gamble, S., 1992, Inhibition of class I and class II MHC-restricted antigen presentation by cytotoxic T lymphocytes specific for an exogenous antigen, J. Immunol. 148:3028–3033.

    PubMed  CAS  Google Scholar 

  • Rock, K. L., Rothstein, L., Gamble, S., and Fleischacker, C., 1993, Characterization of antigen-presenting cells that present exogenous antigens in association with class I MHC molecules, J. Immunol. 150:438–446.

    PubMed  CAS  Google Scholar 

  • Roeder, S., and Fink, G., 1983, The yeast transposon, Ty, in: Mobile Genetic Elements (J. A. Shapiro, ed.), Academic Press, New York, pp. 299–328.

    Google Scholar 

  • Schultz, M., Zinkernagel, R. M., and Hengartner, H., 1991, Peptide-induced antiviral protection by cytotoxic T cells, Proc. Natl. Acad. Sci. USA 88: 991–993.

    Article  Google Scholar 

  • Stover, C. K., de la Cruz, VF., Fuerst, T. R., Burlein, J. E., Benson, L. A., Bennett, L. T., Bansal, G. P., Young, J. F., Lee, M. H., Hatfull, G. F., Snapper, S. B., Barletta, R. G., Jacobs, J. R., Jr., and Bloom, B. R., 1991, New use of BCG for recombinant vaccines, Nature 351:456–460.

    Article  PubMed  CAS  Google Scholar 

  • Takahashi, H., Takeshita, T., Morein, B., Putney, S., Germain, R. N., and Berzofsky, J. A., 1990, Induction of CD8+ cytotoxic T lymphocytes by immunization with purified HIV-1 envelope protein in ISCOMs, Nature 344:873–875.

    Article  PubMed  CAS  Google Scholar 

  • Ulmer, J. B., Donnelly, J. J., Suezanne, E. P., Rhodes, G. H., Feigner, P. L., Dwarki, V. J., Gromkowski, S. H., Deck, R. R., DeWitt, C. M., Friedman, A., Hawe, L. A., Leander, K. R., Martinez, D., Perry, H. C., Shiver, J. W., Montgomery, D. L., and Liu, M. A., 1993, Heterologous protection against influenza by injection of DNA encoding a viral protein, Science 259:1745–1749.

    Article  PubMed  CAS  Google Scholar 

  • Weber, J. N., Clapham, P. R., Weiss, R. A., Parker, D., Roberts, C., Duncan, J., Weiler, I., Carne, C., Tedder, R. S., Pinching, A. J., and Cheingsong-Popov, R., 1987, Human immunodeficiency virus infection in two cohorts of homosexual men: Neutralizing sera and association of anti-gag antibody with prognosis, Lancet 1:119–122.

    Article  PubMed  CAS  Google Scholar 

  • Weldon, R. A., Erdie, C. R., Oliver, M. G., and Wills, J. W., 1990, Incorporation of chimeric Gag protein into retroviral particles, J. Virol. 64:4303–4310.

    Google Scholar 

  • Williamson, V. M., 1983, Transposable elements in yeast, Int. Rev. Cytol. 83:1–25.

    Article  PubMed  CAS  Google Scholar 

  • Wilson, W., Malim, M. H., Kingsman, A. J., and Kingsman, S. M., 1986, Expression strategies of the yeast retrotransposon Ty: A short sequence directs ribosomal frameshifting, Nucleic Acids Res. 14:7001–7015.

    Article  PubMed  CAS  Google Scholar 

  • Wu, J.-Y., Gardner, B. H., Murphy, C. I., Seals, J. R., Kensil, C. R., Recchia, J., Beltz, G. A., Newman, G. W., and Newman, M. J., 1992, Saponin adjuvant enhancement of antigen-specific immune responses to an experimental HIV-1 vaccine, J. Immunol. 148:1519–1525.

    PubMed  CAS  Google Scholar 

  • Yu, X. F., Yuan, X., Matsuda, Z., Lee, T. H., and Essex, M., 1992, The matrix protein of HIV-1 is required for incorporation of viral envelope protein into mature virus, J. Virol. 66:4966–4971.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. British Bio-technology Ltd., Oxford, OX4 5LY, UK

    Sally E. Adams & Alan J. Kingsman

  2. Department of Biochemistry, Oxford University, Oxford, OX1 3QU, UK

    Alan J. Kingsman

Authors
  1. Sally E. Adams
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alan J. Kingsman
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Genentech, Inc., South San Francisco, California, USA

    Michael F. Powell

  2. Vaxcel, Inc., Norcross, Georgia, USA

    Mark J. Newman

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Springer Science+Business Media New York

About this chapter

Cite this chapter

Adams, S.E., Kingsman, A.J. (1995). Retrovirus and Retrotransposon Particles as Antigen Presentation and Delivery Systems. In: Powell, M.F., Newman, M.J. (eds) Vaccine Design. Pharmaceutical Biotechnology, vol 6. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1823-5_34

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-1823-5_34

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5737-7

  • Online ISBN: 978-1-4615-1823-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation