1887

Abstract

Vaccinia virus (VV) infection induces protective T- and B-cell responses, making recombinants based on VV good candidates for the development of effective vaccines to other viruses. VV recombinants expressing the human immunodeficiency virus (HIV) envelope protein (Env) have been generated in several laboratories and shown to induce anti-HIV cellular and humoral immune responses in vaccinated humans and in chimpanzees. To increase the immunogenicity of the Env antigen, a VV recombinant was generated that expresses a chimeric antigen consisting of the Env protein fused to an immunostimulatory cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF). The chimeric protein retained GM-CSF biological activity when expressed by this recombinant virus (VV-GM-gp120) in cells infected in vitro. Infection of BALB/c mice with VV-GM-gp120 triggered a higher HIV-specific cellular immune response, as measured by interferon-gamma production, than that induced by a VV recombinant expressing the native Env protein. Moreover, although anti-gp120 antibody titres were similar in sera from mice inoculated with either of the VV recombinants, immunization with the recombinant expressing the fusion protein elicited antibodies against a broader spectrum of Env epitopes. These results indicate that HIV Env antigen fusion to GM-CSF provides a means to improve the anti-HIV immune response.

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1999-01-01
2024-04-12
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References

  1. Ahlers J. D., Dunlop N., Ailing D. W., Nara P. L., Berzofsky J. A. 1997; Cytokine-in -adjuvant steering of the immune response phenotype to HIV-1 vaccine constructs. Journal ofImmunology 158:3947–3958
    [Google Scholar]
  2. Chakrabarty S., Robert-Guroff M., Wong-Stall F., Gallo R. C., Moss B. 1986; Expression of the HTLV-III envelope gene by a recombinant vaccinia virus. Nature 320:535–537
    [Google Scholar]
  3. Cooney E. L., McElrath J. M., Corey L., Hu S.-L., Collier A. C., Arditti D., Hoffman M., Coombs R. W., Smith G. E., Greenberg P. D. 1993; Enhanced immunity to human immunodeficiency virus (HIV) envelope elicited by a combined vaccine regime consisting of priming with a vaccinia recombinant expressing HIV envelope and boosting with gp160 protein. Proceedings of the National Academy of Sciences, USA 90:1882–1886
    [Google Scholar]
  4. Disis M. L., Bernhard H., Shiota F. M., Hand S. L., Gralow J. R., Huseby E. S., Gillis S., Cheever M. A. 1996; Granulocyte-macrophage colony-stimulating factor: an effective adjuvant for protein and peptide-based vaccines. Blood 88:202–210
    [Google Scholar]
  5. Dranoff G., Jaffee E., Lazenby A., Golumbek P., Levitsky H., Brose K., Jackson V., Hamada H., Pardoll D., Mulligan R. C. 1993; Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proceedings of the National Academy of Sciences, USA 90:3539–3543
    [Google Scholar]
  6. Earl P. L., Robert-Guroff M., Matthews T. J., Krohn K., London W. T., Moss B. 1989; Isolate- and group-specific immune responses to the envelope protein of human immunodeficiency virus induced by a live recombinant vaccinia virus in macaques. AIDS Research and Human Retroviruses 523–32
    [Google Scholar]
  7. Egan M. A., Pavlat W. A., Tartaglia J., Paoletti E., Weinhold K. J., Clements M. L., Siliciano R. F. 1995; Induction of human immunodeficiency virus type 1 (HIV-1)-specific cytolytic T lymphocyte responses in seronegative adults by a nonreplicating, host-range- restricted canarypox vector (ALVAC) carrying the HIV-1MN env gene. Journal of Infectious Diseases 171:1623–1627
    [Google Scholar]
  8. Ellem K. A., O’Rourke M. G., Johnson G. R., Parry G., Misko I. S., Schmidt C. W., Parsons P. G., Burrows S. R., Cross S., Fell A., Li C. L., Bell J. R., Dubois P. J., Moss D. J., Good M. F., Kelso A., Cohen L. K., Dranoff G., Mulligan R. C. 1997; A case report: immune responses and clinical course of the first human use of granulocyte/macrophage-colony-stimulating-factor-transduced autologous melanoma cells for immunotherapy. Cancer Immunology Immunotherapy 44:10–20
    [Google Scholar]
  9. Fenner F., Henderson D. A., Arita I., Jezek Z., Ladnyi I. D. 1988 Smallpox and Its Eradication Geneva: World Health Organization;
    [Google Scholar]
  10. Fleury B., Janvier G., Pialoux G., Buseyne F., Robertson M. N., Tartaglia J., Paoletti E., Kieny M. P., Excler J. L., Riviere Y. 1996; Memory cytotoxic T lymphocyte responses in human immunodeficiency virus type 1 (HIV-1)-seronegative volunteers immunized with a recombinant canarypox expressing gp160 of HIV-1 and boosted with a recombinant gp160. Journal of Infectious Diseases 174:734–738
    [Google Scholar]
  11. Goudsmit J., Back N. K. T., Nara P. L. 1991; Genomic diversity and antigenic variation of HIV-1: links between pathogenesis, epidemiology and vaccine development. FASEB Journal 5:2427–2436
    [Google Scholar]
  12. Gough N. M., Gough J., Metcalf D., Kelso A., Grail D., Nicola N. A., Burgess A. W., Dunn A. R. 1984; Molecular cloning of cDNA encoding a murine haematopoietic growth regulator, granulocyte- macrophage colony stimulating factor. Nature 309:763–767
    [Google Scholar]
  13. Grabstein K., Mochizuki D., Kronheim S., Price V., Cosman D., Urdal D., Gillis S., Conlon P. 1986; Regulation of antibody production in vitro by granulocyte-macrophage colony stimulating factor. Journal of Molecular and Cellular Immunology 2:199–207
    [Google Scholar]
  14. Graham B. S., Matthews T. J., Belshe R. B., Clements M. L., Dolin R., Wright P. F., Gorse G. J., Schwartz D. H., Keefer M. C., Bolognesi D. P., Corey L., Stablein D. M., Esterliz J. R., Hu S. L., Smith G. E., Fast P. E., Koff W. C. 1993; Augmentation of human immunodeficiency virus type 1 neutralizing antibody by priming with gp160 recombinant vaccinia and boosting with rgp160 in vaccinia-naive adults. The NIAD AIDS Vaccine Clinical Trials Network. Journal of Infectious Diseases 167:533–537
    [Google Scholar]
  15. Ho D. D., Sarngadharan M. G., Hirsch M. S., Schooley R. T., Rota T. R., Kennedy R. C., Chanh T. C., Sato V. L. 1987; immunodeficiency virus neutralizing antibodies recognize several conserved domains on the envelope glycoproteins. Journal of Virology 61:2024–2028
    [Google Scholar]
  16. Hu S. L., Kosowski S. G., Dalrymple J. M. 1986; Expression of AIDS virus envelope gene in recombinant vaccinia viruses. Nature 320:537–539
    [Google Scholar]
  17. Kim J. J., Ayyavoo V., Bagarazzi M. L., Chattergoon M. A., Dang K., Wang B., Boyer J. D., Weiner D. B. 1997; In vivo engineering of a cellular immune response by coadministration of IL-12 expression vector with a DNA immunogen. Journal of Immunology 158:816–826
    [Google Scholar]
  18. Luzuriaga K., Sullivan J. L. 1993; HIV-1 specific CTL in long-term survivors of vertical infection. Journal of Cellular Biochemistry Supplement 17E:98
    [Google Scholar]
  19. McElrath M. J., Corey L., Berger D., Hoffman M. C., Klucking S., Dragavon J., Peterson R., Greenberg P. D. 1994; Immune responses elicited by recombinant vaccinia-human immunodeficiency virus (HIV) envelope and HIV envelope proteins: analysis of the durability of responses and effect of repeated boosting. Journal of Infectious Diseases 169:41–47
    [Google Scholar]
  20. Metcalf D. 1986; The molecular biology and functions of the granulocyte-macrophage colony-stimulating factors. Blood 67:257–267
    [Google Scholar]
  21. Miyahira Y., Murata K., Rodriguez D., Rodriguez J. R., Esteban M., Rodrigues M. M., Zavala F. 1995; Quantification of antigen specific CD8+ T cells using an ELISPOT assay. Journal of Immunological Methods 181:45–54
    [Google Scholar]
  22. Morrissey P. J., Bressler L., Park L. S., Alpert A., Gillis S. 1987; Granulocyte-macrophage colony-stimulating factor augments the primary antibody response by enhancing the function of antigen-presenting cells. Journal of Immunology 139:1113–1119
    [Google Scholar]
  23. Moss B. 1996; Genetically engineered poxviruses for recombinant gene expression, vaccination, and safety. Proceedings of the National Academy of Sciences, USA 93:11341–11348
    [Google Scholar]
  24. Paoletti E. 1996; Applications of poxvirus vectors to vaccination: an update. Proceedings of the National Academy of Sciences, USA 93:11349–11353
    [Google Scholar]
  25. Pialoux G., Excler J.-L., Riviere Y., Gonzalez-Canali G., Feuillie V., Coulaud P., Gluckman J.-C., Matthews T. J., Meignier B., Kieny M.-P., Gonnet P., Diaz I., Meric C., Paoletti E., Tartaglia J., Salomon H., Plotkin S. 1995; A prime-boost approach to HIV preventive vaccine using a recombinant canarypox virus expressing glycoprotein 160 (MN) followed by a recombinant glycoprotein 160 (MN/LAI). AIDS Research and Human Retroviruses 11:373–381
    [Google Scholar]
  26. Rodríguez D., Rodriguez J. R., Rodriguez J. F., Trauber D., Esteban M. 1989; Highly attenuated vaccinia virus mutants for the generation of safe recombinant viruses. Proceedings ofthe NationalAcademy of Sciences, USA 86:1287–1291
    [Google Scholar]
  27. Sallusto F., Lanzavecchia A. 1994; Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte-macrophage colony-stimulating factor plus interleukin-4 and down- regulated by tumor necrosis factor-a. Journal of Experimental Medicine 179:1109–1118
    [Google Scholar]
  28. Smith P. D., Lamerson C. L., Wong H. L., Wahl L. M., Wahl S. M. 1990; Granulocyte-macrophage colony-stimulating factor stimulates human monocyte accessory cell function. Journal of Immunology 144:3829–3834
    [Google Scholar]
  29. Steinman R. 1991; The dendritic cell system and its role in immunogenicity. Annual Review of Immunology 9:271–296
    [Google Scholar]
  30. Tao M. H., Levy R. 1993; Idiotype/granulocyte-macrophage colony-stimulating factor fusion protein as a vaccine for B-cell lymphoma. Nature 362:755–758
    [Google Scholar]
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