Abstract
T-cells play a crucial role in the control of various viral infections such as HIV and herpes viruses. Thus, the development of advanced techniques for the stimulation and measurement of both antigen-specific T-helper and CTL responses is one of most meaningful objectives in vaccinology. Herein, we present HIV-1 Pr55gag lipoprotein particles (VLPs) to be a potent antigen for introducing epitopes into the MHC-class-I and -II processing and presentation pathway. These VLPs can easily be produced in insect cells by using the baculovirus expression system. Immunization studies in mice revealed the strong capacity of these VLPs to stimulate Gag-specific T-helper-1 cell-biased humoral and cellular immune responses. In addition, these VLPs can be used as a stimulator antigen for the detection of Gag-specific T-helper and CTL responses, as determined by conventional ELISA, ELISpot, FACS, and 51Cr-release assays. These results strongly underline the value of VLPs as a stimulator of MHC-class-I and -II mediated epitope presentation for preventive, therapeutic, and diagnostic purposes.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Rook, A. H. (1988) Interactions of cytomegalovirus with the human immune system. Rev. Infect. Dis. 10, 460ā467.
Arvin, A. M. (1992) Cell-mediated immunity to varicella-zoster virus. J. Infect. Dis. 166, 35ā41.
Simmons, A. and Tscharke, D. C. (1992) Anti-CD8 impairs clearance of herpes simplex virus from the nervous system: implications for the fate of virally infected neurons. J. Exp. Med. 175, 1337ā1344.
Gotch, F., Gallimore, A., and McMichael, A. (1996) Cytotoxic T cellsāprotection from disease progressionāprotection from infection. Immunol. Lett. 51, 125ā128.
Khanna, R., Moss, D. J., and Burrows, S. R. (1999) Vaccine strategies against Epstein-Barr virus-associated diseases: lessons from studies on cytotoxic T-cell-mediated immune regulation. Immunol. Rev. 170, 49ā64.
Khanna, R. and Burrows, S. R. (2000) Role of cytotoxic T lymphocytes in Epstein-Barr virus-associated diseases. Annu. Rev. Microbiol. 54, 19ā48.
Pantaleo, G., Demarest, J. F., Soudeyns, H., et al. (1994) Major expansion of CD8+ T cells with a predominant V beta usage during the primary immune response to HIV. Nature 370, 463ā467.
Koup, R. A., Safrit, J. T., Cao, Y., et al. (1994) Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J. Virol. 68, 4650ā4655.
Rinaldo, C., Huang, X. L., Fan, Z. F., et al. (1995) High levels of anti-human immunodeficiency virus type 1 (HIV-1) memory cytotoxic T-lymphocyte activity and low viral load are associated with lack of disease in HIV-1-infected long-term nonprogressors. J. Virol. 69, 5838ā5842.
Koup, R. A. and Ho, D. D. (1994) Shutting down HIV. Nature 370, 416.
Safrit, J. T., Andrews, C. A., Zhu, T., Ho, D. D., and Koup, R. A. (1994) Characterization of human immunodeficiency virus type 1-specific cytotoxic T lymphocyte clones isolated during acute seroconversion: recognition of autologous virus sequences within a conserved immunodominant epitope. J. Exp. Med. 179, 463ā472.
Klein, M., Van Baalen, C., Holwerda, A., et al. (1995) Kinetics of Gag-specific cytotoxic T lymphocyte responses during the clinical course of HIV-1 infection: a longitudinal analysis of rapid progressors and long-term asymptomatics. J. Exp. Med. 181, 1365ā1372.
Betts, M. R., Krowka, J., Santamaria, C., et al. (1997) Cross-clade human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte responses in HIV-infected Zambians. J. Virol. 71, 8908ā8911.
Durali, D., Morvan, J., Letourneur, F., et al. (1998) Cross-reactions between the cytotoxic T-lymphocyte responses of human immunodeficiency virus-infected African and European patients. J. Virol. 72, 3547ā3553.
Lynch, J. A., deSouza, M., Robb, M. D., et al. (1998) Cross-clade cytotoxic T cell response to human immunodeficiency virus type 1 proteins among HLA disparate North Americans and Thais. J. Infect. Dis. 178, 1040ā1046.
Wagner, R., Leschonsky, B., Harrer, E., et al. (1999) Molecular and functional analysis of a conserved CTL epitope in HIV-1 p24 recognized from a long-term nonprogressor: constraints on immune escape associated with targeting a sequence essential for viral replication. J. Immunol. 162, 3727ā3734.
Cox, J. C. and Coulter, A. R. (1997) Adjuvantsāa classification and review of their modes of action. Vaccine 15, 248ā256.
Gustafson, G. L. and Rhodes, M. J. (1992) Bacterial cell wall products as adjuvants: early interferon gamma as a marker for adjuvants that enhance protective immunity. Res. Immunol. 143, 483ā488.
Wu, J. Y., Gardner, B. H., Murphy, C. I., et al. (1992) Saponin adjuvant enhancement of antigen-specific immune responses to an experimental HIV-1 vaccine. J. Immunol. 148, 1519ā1525.
Ke, Y., Li, Y., and Kapp, J. A. (1995) Ovalbumin injected with complete Freundās adjuvant stimulates cytolytic responses. Eur. J. Immunol. 25, 549ā553.
Schulz, M., Zinkernagel, R. M., and Hengartner, H. (1991) Peptide-induced antiviral protection by cytotoxic T cells. Proc. Natl. Acad. Sci. USA 88, 991ā993.
Takahashi, H., Takeshita, T., Morein, B., Putney, S., Germain, R. N., and Berzofsky, J. A. (1990) Induction of CD8+ cytotoxic T cells by immunization with purified HIV-1 envelope protein in ISCOMs. Nature 344, 873ā875.
Zhou, F., Rouse, B. T., and Huang, L. (1992) Prolonged survival of thymoma-bearing mice after vaccination with a soluble protein antigen entrapped in liposomes: a model study. Cancer Res. 52, 6287ā6291.
Maloy, K. J., Donachie, A. M., OāHagan, D. T., and Mowat, A. M. (1994) Induction of mucosal and systemic immune responses by immunization with ovalbumin entrapped in poly(lactide-co-glycolide) microparticles. Immunology 81, 661ā667.
VanCott, T. C., Kaminski, R. W., Mascola, J. R., et al. (1998) HIV-1 neutralizing antibodies in the genital and respiratory tracts of mice intranasally immunized with oligomeric gp160. J. Immunol. 160, 2000ā2012.
von Brunn, A., Fruh, K., Muller, H. M., Zentgraf, H. W., and Bujard, H. (1991) Epitopes of the human malaria parasite P. falciparum carried on the surface of HBsAg particles elicit an immune response against the parasite. Vaccine 9, 477ā484.
Schlienger, K., Mancini, M., Riviere, Y., Dormont, D., Tiollais, P., and Michel, M. L. (1992) Human immunodeficiency virus type 1 major neutralizing determinant exposed on hepatitis B surface antigen particles is highly immunogenic in primates. J. Virol. 66, 2570ā2576.
Michel, M. L., Mancini, M., Schlienger, K., and Tiollais, P. (1993) Recombinant hepatitis B surface antigen as a carrier of human immunodeficiency virus epitopes. Res. Virol. 144, 263ā267.
Schirmbeck, R., Melber, K., Kuhrober, A., Janowicz, Z. A., and Reimann, J. (1994) Immunization with soluble hepatitis B virus surface protein elicits murine H-2 class I-restricted CD8+ cytotoxic T lymphocyte responses in vivo. J. Immunol. 152, 1110ā1113.
Breitburd, F., Kirnbauer, R., Hubbert, N. L., et al. (1995) Immunization with viruslike particles from cottontail rabbit papillomavirus (CRPV) can protect against experimental CRPV infection. J. Virol. 69, 3959ā3963.
Kirnbauer, R. (1996) Papillomavirus-like particles for serology and vaccine development. Intervirology 39, 54ā61.
Sedlik, C., Saron, M., Sarraseca, J., Casal, I., and 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. USA 94, 7503ā7508.
Lo-Man, R., Rueda, P., Sedlik, C., Deriaud, E., Casal, I., and 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, 1401ā1407.
Griffiths, J. C., Berrie, E. L., Holdsworth, L. N., et al. (1991) Induction of high-titer neutralizing antibodies, using hybrid human immunodeficiency virus V3-Ty viruslike particles in a clinically relevant adjuvant. J. Virol. 65, 450ā456.
Harris, S. J., Gearing, A. J., Layton, G. T., Adams, S. E., and Kingsman, A. J. (1992) Enhanced proliferative cellular responses to HIV-1 V3 peptide and gp120 following immunization with V3ā¶Ty virus-like particles. Immunology 77, 315ā321.
Delchambre, M., Gheysen, D., Thines, D., et al. (1989) The GAG precursor of simian immunodeficiency virus assembles into virus-like particles. EMBO J. 8, 2653ā2660.
Wills, J. W. and Craven, R. C. (1991) Form, function, and use of retroviral gag proteins. AIDS 5, 639ā654.
Gheysen, D., Jacobs, E., de Foresta, F., et al. (1989) Assembly and release of HIV-1 precursor Pr55gag virus-like particles from recombinant baculovirus-infected insect cells. Cell 59, 103ā112.
Vernon, S. K., Murthy, S., Wilhelm, J., et al. (1991) Ultrastructural characterization of human immunodeficiency virus type 1 Gag-containing particles assembled in a recombinant adenovirus vector system. J. Gen. Virol. 72, 1243ā1251.
Royer, M., Cerutti, M., Gay, B., Hong, S. S., Devauchelle, G., and Boulanger, P. (1991) Functional domains of HIV-1 gag-polyprotein expressed in baculovirus-infected cells. Virology 184, 417ā422.
Wagner, R., Fliessbach, H., Wanner, G., et al. (1992) Studies on processing, particle formation, and immunogenicity of the HIV-1 gag gene product: a possible component of a HIV vaccine. Arch. Virol. 127, 117ā137.
Wagner, R., Deml, L., Schirmbeck, R., Niedrig, M., Reimann, J., and Wolf, H. (1996) Construction, expression and immunogenicity of chimeric HIV-1 virus-like particles. Virology 220, 128ā140.
Deml, L., Schirmbeck, R., Reimann, J., Wolf, H., and Wagner, R. (1997) Recombinant human immunodeficiency Pr55gag virus-like particles presenting chimeric envelope glycoproteins induce cytotoxic T-cells and neutralizing antibodies. Virology 235, 26ā39.
Wolf, H., Modrow, S., Soutschek, E., Motz, M., Grunow, R., and Dƶbl, H. (1990) Production, mapping and biological characterisation of monoclonal antibodies to the core protein (p24) of the human immunodeficiency virus type 1. AIFO 1, 24ā29.
Deml, L., Kratochwil, G., Osterrieder, N., Knuchel, R., Wolf, H., and Wagner, R. (1997) Increased incorporation of chimeric human immunodeficiency virus type 1 gp120 proteins into Pr55gag virus-like particles by an Epstein-Barr virus gp220/350-derived transmembrane domain. Virology 235, 10ā25.
Wagner, R., Teeuwsen, V. J., Deml, L., et al. (1998) Cytotoxic T cells and neutralizing antibodies induced in rhesus monkeys by virus-like particle HIV vaccines in the absence of protection from SHIV infection. Virology 245, 65ā74.
Paliard, X., Liu, Y., Wagner, R., Wolf, H., Baenziger, J., and Walker, C. M. (2000) Priming of strong, broad, and long-lived HIV type 1 p55gag-specific CD8+ cytotoxic T cells after administration of a virus-like particle vaccine in rhesus macaques. AIDS Res. Hum Retroviruses 16, 273ā282.
Ogg, G. S., Jin, X., Bonhoeffer, S., et al. (1998) Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA. Science 279, 2103ā2106.
Betts, M. R., Casazza, J. P., Patterson, B. A., et al. (2000) Putative immunodominant human immunodeficiency virus-specific CD8(+) T-cell responses cannot be predicted by major histocompatibility complex class I haplotype. J. Virol. 74, 9144ā9151.
Zajac, A. J., Murali-Krishna, K., Blattman, J. N., and Ahmed, R. (1998) Therapeutic vaccination against chronic viral infection: the importance of cooperation between CD4+ and CD8+ T cells. Curr. Opin. Immunol. 10, 444ā449.
Waldrop, S. L., Pitcher, C. J., Peterson, D. M., Maino, V. C., and Picker, L. J. (1997) Determination of antigen-specific memory/effector CD4+ T cell frequencies by flow cytometry: evidence for a novel, antigen-specific homeostatic mechanism in HIV-associated immunodeficiency. J. Clin. Invest. 99, 1739ā1750.
Sester, M., Sester, U., Kohler, H., et al. (2000) Rapid whole blood analysis of virus-specific CD4 and CD8 T cell responses in persistent HIV infection. AIDS 14, 2653ā2668.
Heintel, T., Sester, M., Rodriguez, M. M., et al. (2002) The fraction of perforin-expressing HIV-specific CD8 T cells is a marker for disease progression in HIV infection. AIDS 16, 1497ā1501.
Sambrook, J., Fritsch, E. F., and Maniatis, T. (1989) Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
Qiu, J. T., Song, R., Dettenhofer, M., et al. (1999) Evaluation of novel human immunodeficiency virus type 1 Gag DNA vaccines for protein expression in mammalian cells and induction of immune responses. J. Virol. 73, 9145ā9152.
Takahashi, H., Cohen, J., Hosmalin, A., et al. (1988) An immunodominant epitope of the human immunodeficiency virus envelope glycoprotein gp160 recognized by class I major histocompatibility complex molecule-restricted murine cytotoxic T lymphocytes. Proc. Natl. Acad. Sci. USA 85, 3105ā3109.
White, B. A. (1993) Methods in Molecular Biology: PCR Protocols, Current Methods and Applications. Humana, Totowa, NJ.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
Ā© 2004 Humana Press Inc.
About this protocol
Cite this protocol
Deml, L., Wild, J., Wagner, R. (2004). Virus-like Particles. In: Decler, J., Reischl, U. (eds) Molecular Diagnosis of Infectious Diseases. Methods in Molecular Medicineā¢, vol 94. Humana Press. https://doi.org/10.1385/1-59259-679-7:133
Download citation
DOI: https://doi.org/10.1385/1-59259-679-7:133
Publisher Name: Humana Press
Print ISBN: 978-1-58829-221-6
Online ISBN: 978-1-59259-679-9
eBook Packages: Springer Protocols