1887

Abstract

The minimum requirement for candidate human immunodeficiency virus (HIV) vaccines to enter clinical evaluation in humans should be their demonstrable immunogenicity in non-human primates: induction of antibodies neutralizing primary HIV isolates or elicitation of broad T cell-mediated immune responses. Here, we showed in rhesus macaques that the very same vaccines that had entered clinical trials in Oxford and Nairobi, plasmid pTHr.HIVA DNA and recombinant modified vaccinia virus Ankara MVA.HIVA in a prime-boost protocol (Hanke & McMichael, 6, 951–955, 2000), induced cellular immune responses specific for multiple HIV-derived epitopes. This was demonstrated by using the intracellular cytokine staining and ELISPOT assays detecting interferon-γ and pools of peptides employed in the clinical studies. These results have both boosted our expectations for the performance of these vaccines in humans and increased our confidence about the choice of these assays as the primary readouts in the on-going human trials.

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2002-01-01
2024-04-19
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References

  1. Allen T. M., Sidney J., del Guercio M.-F., Glickman R. L., Lensmeyer G. L., Wiebe D. A., Pauza C. D., Johnson R. P., Sette A., Watkins D. I. 1998; Characterization of the peptide-binding motif of a rhesus MHC class I molecule (Mamu-A*01) that binds an immunodominant CTL epitope from SIV. Journal of Immunology 160:6062–6071
    [Google Scholar]
  2. Allen T. M., Vogel T. U., Fuller D. H., Monthe B. R., Steffen S., Boyson J. E., Shipley T., Fuller J., Hanke T., Sette A., Altman J. D., Moss B., McMichael A. J., Watkins D. I. 2000; Induction of AIDS virus-specific CTL activity in fresh, unstimulated peripheral blood lymphocytes from rhesus macaques vaccinated with a DNA prime/modified vaccinia virus Ankara boost regimen. Journal of Immunology 164:4968–4978
    [Google Scholar]
  3. Amara R. R., Villinger F., Altman J. D., Lydy S. L., O’Neil S. P., Staprans S. I., Montefiori D. C., Xu Y., Herndon J. G., Wyatt L. S., Candido M. A., Kozyr N. L., Earl P. L., Smith J. M., Ma H. L., Grimm B. D., Hulsey M. L., Miller J., McClure H. M., McNicholl J. M., Moss B., Robinson H. L. 2001; Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA/MVA vaccine. Science 292:69–74
    [Google Scholar]
  4. Barouch D. H., Santra S., Schmitz J. E., Kuroda M. J., Fu T. M., Wagner W., Bilska M., Craiu A., Zheng X. X., Krivulka G. R., Beaudry K., Lifton M. A., Nickerson C. E., Trigona W. L., Punt K., Freed D. C., Guan L., Dubey S., Casimiro D., Simon A., Davies M. E., Chastain M., Strom T. B., Gelman R. S., Montefiori D. C., Lewis M. G., Letvin N. L. 2000; Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination. Science 290:486–492
    [Google Scholar]
  5. Blaney J. E. J., Nobusawa E., Brehm M. A., Bonneau R. H., Mylin L. M., Fu T. M., Kawaoka Y., Tevethia S. S. 1998; Immunization with a single major histocompatibility complex class I-restricted cytotoxic T-lymphocyte recognition epitope of herpes simplex virus type 2 confers protective immunity. Journal of Virology 72:9567–9574
    [Google Scholar]
  6. Borrow P., Lewicki H., Hahn B. E., Shaw G. M., Oldstone M. B. 1994; Virus-specific CD8+ CTL activity associated with control of viremia in primary HIV-1 infection. Journal of Virology 68:6103–6110
    [Google Scholar]
  7. Borrow P., Lewicki H., Wei X., Horwitz M. S., Peffer N., Meyers H., Nelson J. A., Gairin J. E., Hahn B. H., Oldstone M. B. A., Shaw G. M. 1997; Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus. Nature Medicine 3:205–211
    [Google Scholar]
  8. Fu T. M., Guan L., Friedman A., Schofield T. L., Ulmer J. B., Liu M. A., Donnelly J. J. 1999; Dose dependence of CTL precursor frequency induced by a DNA vaccine and correlation with protective immunity against influenza virus challenge. Journal of Immunology 162:4163–4170
    [Google Scholar]
  9. Gallimore A., Cranage M., Cook N., Almond N., Bootman J., Rud R., Silvera P., Dennis M., Corcoran T., Stott J., McMichael A., Gotch F. 1995; Early suppression of SIV replication by CD8+ nef-specific cytotoxic T cells in vaccinated animals. Nature Medicine 1:1167–1173
    [Google Scholar]
  10. Goulder P. J. R., Phillips R. E., Colbert R. A., McAdam S., Ogg G., Nowak M. A., Giangrande P., Luzzi G., Morgan B., Edwards A., McMichael A. J., Rowland-Jones S. 1997; Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS. Nature Medicine 3:212–217
    [Google Scholar]
  11. Haas G., Plikat U., Debre P., Lucchiari M., Katlama C., Dudoit Y., Bonduelle O., Bauer M., Ihlenfeldt H. G., Jung G., Maier B., Meyerhans A., Autran B. 1996; Dynamics of viral variants in HIV-1 Nef and specific cytotoxic T lymphocytes in vivo. Journal of Immunology 157:4212–4221
    [Google Scholar]
  12. Hanke T. 2001; Prospect of a prophylactic vaccine for HIV. British Medical Bulletin 58: (in press)
    [Google Scholar]
  13. Hanke T., McMichael A. J. 2000; Design and construction of an experimental HIV-1 vaccine for a year-2000 clinical trial in Kenya. Nature Medicine 6:951–955
    [Google Scholar]
  14. Hanke T., Blanchard T. J., Schneider J., Hannan C. M., Becker M., Gilbert S. C., Hill A. V. S., Smith G. L., McMichael A. 1998a; Enhancement of MHC class I-restricted peptide-specific T cell induction by a DNA prime/MVA boost vaccination regime. Vaccine 16:439–445
    [Google Scholar]
  15. Hanke T., Schneider J., Gilbert S. C., Hill A. V. S., McMichael A. 1998b; DNA multi-CTL epitope vaccines for HIV and Plasmodium falciparum : Immunogenicity in mice. Vaccine 16:426–435
    [Google Scholar]
  16. Hanke T., Neumann V. C., Blanchard T. J., Becker M., Sweeney P., Hill A. V. S., Smith G. L., McMichael A. 1999a; Effective induction of HIV-specific CTL by multi-epitope DNA using a gene gun in a combined vaccination regime. Vaccine 17:589–596
    [Google Scholar]
  17. Hanke T., Samuel R. V., Blanchard T. J., Neumann V. C., Allen T. M., Boyson J. E., Sharpe A. S., Cook N., Smith G. L., Watkins D. I., Cranage M. P., McMichael A. 1999b; Effective induction of simian immunodeficiency virus-specific cytotoxic T lymphocytes in macaques by using a multiepitope gene and DNA prime-modified vaccinia virus Ankara boost vaccination regimen. Journal of Virology 73:7524–7532
    [Google Scholar]
  18. Jin X., Bauer D. E., Tuttleton S. E., Lewin S., Gettie A., Blanchard J., Irwin C. E., Safrit J. T., Mittler J., Weinberger L., Kostrikis L. G., Zhang L., Perelson A. S., Ho D. D. 1999; Dramatic rise in plasma viremia after CD8+T cell depletion in simian immunodeficiency virus-infected macaques. Journal of Experimental Medicine 189:991–998
    [Google Scholar]
  19. Kent S. J., Woodward A., Zhao A. 1997; Human immunodeficiency virus type 1 (HIV-1)-specific T cell responses correlate with the control of acute HIV-1 infection in macaques. Journal of Infectious Diseases 176:1188–1197
    [Google Scholar]
  20. Kent S. J., Zhao A., Best S. J., Chandler J. D., Boyle D. B., Ramshaw I. A. 1998; Enhanced T-cell immunogenicity and protective efficacy of a human immunodeficiency virus type 1 vaccine regimen consisting of consecutive priming with DNA and boosting with recombinant fowlpox virus. Journal of Virology 72:10180–10188
    [Google Scholar]
  21. Koenig S., Conley A. J., Brewah Y. A., Jones G. M., Leath S., Boots L. J., Davey V., Pantaleo G., Demarest J. F., Carter C. and others 1995; Transfer of HIV-1-specific cytotoxic T lymphocytes to an AIDS patient leads to selection for mutant HIV variants and subsequent disease progression. Nature Medicine 1:330–336
    [Google Scholar]
  22. Koup R. A., Safrit J. T., Cao Y., Andrews C. A., McLeod G., Borkowsky W., Farthing C., Ho D. D. 1994; Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. Journal of Virology 68:4650–4655
    [Google Scholar]
  23. Maino V. C., Picker L. J. 1998; Identification of functional subsets by flow cytometry: intracellular detection of cytokine expression. Cytometry 34:518–525
    [Google Scholar]
  24. Matloubian M., Concepcion R. J., Ahmed R. 1994; CD4+ T cells are required to sustain CD8+ cytotoxic T-cell responses during chronic viral infection. Journal of Virology 68:8056–8063
    [Google Scholar]
  25. Miller M. D., Yamamoto H., Hughes A. L., Watkins D. I., Letvin N. L. 1991; Definition of an epitope and MHC class I molecule recognized by Gag-specific cytotoxic T lymphocytes in SIVmac-infected rhesus monkeys. Journal of Immunology 147:320–329
    [Google Scholar]
  26. Phillips R. E., Rowland-Jones S., Nixon D. F., Gotch F. M., Edwards J. P., Ogunlesi A. O., Elvin J. G., Rothbard J. A., Bangham C. R., Rizza C. R., McMichael A. J. 1991; Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition. Nature 354:453–459
    [Google Scholar]
  27. Price D. A., Goulder P. J., Klenerman P., Sewell A. K., Easterbrook P. J., Troop M., Bangham C. R., Phillips R. E. 1997; Positive selection of HIV-1 cytotoxic T lymphocyte escape variants during primary infection. Proceedings of the National Academy of Sciences, USA 94:1890–1895
    [Google Scholar]
  28. Price D. A., Sewell A. K., Dong T., Tan R., Goulder P. J., Rowland-Jones S. L., Phillips R. E. 1998; Antigen-specific release of beta-chemokines by anti-HIV-1 cytotoxic T lymphocytes. Current Biology 8:355–358
    [Google Scholar]
  29. Robinson H. L., Montefiori D. C., Johnson R. P., Manson K. H., Kalish M. L., Lifson J. D., Rizvi T. A., Lu S., Hu S.-L., Mazzara G. P., Panicali D. L., Herndon J. G., Glickman R., Candido M. A., Lydy S. L., Wyand M. S., McClure H. M. 1999; Neutralizing antibody-independent containment of immunodeficiency virus challenges by DNA priming and recombinant pox virus booster immunizations. Nature Medicine 5:526–534
    [Google Scholar]
  30. Rosenberg E. S., LaRosa L., Flynn T., Robbins G., Walker B. D. 1999; Characterization of HIV-1-specific T-helper cells in acute and chronic infection. Immunology Letters 66:89–93
    [Google Scholar]
  31. Rowland-Jones S. L., McMichael A. 1995; Immune responses in HIV-exposed seronegatives: have they repelled the virus?. Current Opinion in Immunology 7:448–455
    [Google Scholar]
  32. Schmitz J. E., Kuroda M. J., Sasseville V. G., Simon M. A., Lifton M. A., Racz P., Tenner-Racz K., Dalesandro M., Scallon B. J., Ghrayeb J., Forman M. A., Montefiori D. C., Rieber E. P., Letvin N. L., Reinmann K. A. 1999; Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 283:857–860
    [Google Scholar]
  33. Schneider J., Gilbert S. C., Blanchard T. J., Hanke T., Robson K. J., Hannan C. M., Becker M., Sinden R., Smith G. L., Hill A. V. S. 1998; Enhanced immunogenicity for CD8+ T cell induction and complete protective efficacy of malaria DNA vaccination by boosting with modified vaccinia virus Ankara. Nature Medicine 4:397–402
    [Google Scholar]
  34. Stranford S. A., Skurnick J., Louria D., Osmond D., Chang S. Y., Sninsky J., Ferrari G., Weinhold K., Lindquist C., Levy J. A. 1999; Lack of infection in HIV-exposed individuals is associated with a strong CD8+ cell noncytotoxic anti-HIV response. Proceedings of the National Academy of Sciences, USA 96:1030–1035
    [Google Scholar]
  35. Suni M. A., Picker L. J., Maino V. C. 1998; Detection of antigen-specific T cell cytokine expression in whole blood by flow cytometry. Journal of Immunological Methods 212:89–98
    [Google Scholar]
  36. Tan L. C., Gudgeon N., Annels N. E., Hansasuta P., O’Callaghan C. A., Rowland-Jones S., McMichael A. J., Rickinson A. B., Callan M. F. 1999; A re-evaluation of the frequency of CD8+ T cells specific for EBV in healthy virus carriers. Journal of Immunology 162:1827–1835
    [Google Scholar]
  37. von Herrath M. G., Yokoyama M., Dockter J., Oldstone M. B., Whitton J. L. 1996; CD4-deficient mice have reduced levels of memory cytotoxic T lymphocytes after immunization and show diminished resistance to subsequent virus challenge. Journal of Virology 70:1072–1079
    [Google Scholar]
  38. Wagner L., Yang O. O., Garcia-Zepeda E. A., Ge Y., Kalams S. A., Walker B. D., Pasternack M. S., Luster A. D. 1998; Beta-chemokines are released from HIV-1-specific cytolytic T cell granules complexed to proteoglycans. Nature 391:908–911
    [Google Scholar]
  39. Wilson C. C., Brown R. C., Korber B. T., Wilkes B. M., Ruhl D. J., Sakamoto D., Kunstman K., Luzuriaga K., Hanson I. C., Widmayer S. M., Wiznia A., Clapp S., Ammann A. J., Koup R. A., Wolinsky S. M., Walker B. D. 1999; Frequent detection of escape from cytotoxic T-lymphocyte recognition in perinatal human immunodeficiency virus (HIV) type 1 transmission: the Ariel Project for the prevention of transmission of HIV from mother to infant. Journal of Virology 73:3975–3985
    [Google Scholar]
  40. Wilson J. D., Ogg G. S., Allen R. L., Davis C., Shaunak S., Downie J., Dyer W., Workman C., Sullivan S., McMichael A. J., Rowland-Jones S. L. 2000; Direct visualization of HIV-1-specific cytotoxic T lymphocytes during primary infection. AIDS 14:225–233
    [Google Scholar]
  41. Wolinsky S. M., Korber B. T., Neumann A. U., Daniels M., Kunstman K. J., Whetsell A. J., Furtado M. R., Cao Y., Ho D. D., Safrit J. T. 1996; Adaptive evolution of human immunodeficiency virus-type 1 during the natural course of infection. Science 272:537–542
    [Google Scholar]
  42. Yang O. O., Kalams S. A., Trocha A., Cao H., Luster A., Johnson R. P., Walker B. D. 1997; Suppression of human immunodeficiency virus type 1 replication by CD8+ cells: evidence for HLA class I-restricted triggering of cytolytic and noncytolytic mechanisms. Journal of Virology 71:3120–3128
    [Google Scholar]
  43. Zhang C., Cui Y., Houston S., Chang L. J. 1996; Protective immunity to HIV-1 in SCID/beige mice reconstituted with peripheral blood lymphocytes of exposed but uninfected individuals. Proceedings of the National Academy of Sciences, USA 93:14720–14725
    [Google Scholar]
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