1887

Abstract

A major aim in AIDS vaccine development is the definition of strategies to stimulate strong and durable cytotoxic T lymphocyte (CTL) responses. Here we report that simian immunodeficiency virus (SIV)-specific CTL developed in 4/4 macaques following a single intramuscular injection of modified vaccinia virus Ankara (MVA) constructs expressing both structural and regulatory/accessory genes of SIV. In two animals Nef-specific responses persisted, but other responses diminished and new responses were not revealed, following further vaccination. Vaccination of another two macaques, expressing Mamu A*01 MHC class I, with MVA constructs containing and under the control of the moderate strength natural vaccinia virus early/late promoter P7.5, again induced an early Nef-specific response, whereas responses to Gag remained undetectable. Anti-vector immunity induced by this immunization was shown to prevent the efficient stimulation of CTL directed to the cognate Gag epitope, p11C C-M, following vaccination with another MVA construct expressing SIV Gag–Pol under a strong synthetic vaccinia virus-specific promoter. In contrast, vaccination of a previously unexposed animal resulted in a SIV-specific CTL response widely disseminated in lymphoid tissues including lymph nodes associated with the rectal and genital routes of SIV entry. Thus, despite the highly attenuated nature of MVA, repeated immunization may elicit sufficient anti-vector immunity to limit the effectiveness of later vaccination.

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2001-09-01
2019-09-18
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References

  1. Allen, T. A., Sidney, J., del Guercio, M.-F., Glickman, R. L., Lensmayer, G. L., Wiebe, D. A., DeMars, R., 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 simian immunodeficiency virus. Journal of Immunology 160, 6062-6071.
    [Google Scholar]
  2. Belyakov, I. M., Wyatt, L. S., Ahlers, J. D., Earl, P., Penleton, C. D., Kelsall, B. L., Strober, W., Moss, B. & Berzofsky, J. A. ( 1998; ). Induction of mucosal CTL response by intrarectal immunization with a replication-deficient recombinant vaccinia virus expressing HIV 89.6 envelope protein. Journal of Virology 72, 8264-8272.
    [Google Scholar]
  3. Belyakov, I. M., Moss, B., Strober, W. & Berzofsky, J. A. ( 1999; ). Mucosal vaccination overcomes the barrier to recombinant vaccinia immunization caused by pre-existing poxvirus immunity. Proceedings of the National Academy of Sciences, USA 96, 4512-4517.[CrossRef]
    [Google Scholar]
  4. Bennink, J. R., Yewdell, J. W., Smith, G. L. & Moller, C. ( 1984; ). Recombinant vaccinia virus primes and stimulates influenza haemagglutinin-specific cytotoxic T cells. Nature 311, 578-579.[CrossRef]
    [Google Scholar]
  5. Benson, J., Chougnet, C., Robert-Guroff, M., Montefiori, D., Markham, P., Shearer, G., Gallo, R. C., Cranage, M., Paoletti, E., Limbach, K., Venzon, D., Tartaglia, J. & Franchini, G. ( 1998; ). Recombinant vaccine-induced protection against the highly pathogenic simian immunodeficiency virus SIVmac251: dependence on route of challenge exposure. Journal of Virology 72, 4170-4182.
    [Google Scholar]
  6. Chakrabarti, S., Sisler, J. R. & Moss, B. ( 1997; ). Compact, synthetic, vaccinia virus early/late promoter for protein expression. Biotechniques 23, 1094-1097.
    [Google Scholar]
  7. Cooney, E. L., Collier, A. C., Greenberg, P. D., Coombs, R. W., Zarling, J., Arditti, D. E., Hoffman, M. C., Hu, S.-L. & Corey, L. ( 1991; ). Safety of and immunological response to a recombinant vaccinia virus vaccine expressing HIV envelope glycoprotein. Lancet 337, 567-572.[CrossRef]
    [Google Scholar]
  8. Cranage, M., Polyanskaya, N., Cook, N., Leech, S., Ashworth, T., Sharpe, S., Teng, X.-C., Dennis, M., Hall, G., Greenaway, P., Stott, J., Chan, L., Kent, K., Almond, N., Spitali, M., Rhodes, A., Hutchinson, G., Stephens, P., Mackett, M. & Rud, E. ( 1994; ). Immune responses to both cellular and viral proteins can mediate protection against infection with SIVmac. In Vaccines 94 , pp. 203-209. Edited by N. Norrby, F. Brown, R. M. Chanock & H. S. Ginsberg. Cold Spring Harbor, NY:Cold Spring Harbor Laboratory.
  9. Gallimore, A., Cranage, M., Cook, N., Almond, N., Bootman, J., Rud, E., 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 macaques. Nature Medicine 1, 1167-1173.[CrossRef]
    [Google Scholar]
  10. Goulder, J. R., Rowland-Jones, S. L., McMichael, A. J. & Walker, B. D. ( 1999; ). Anti-HIV cellular immunity: recent advances towards vaccine design. AIDS 13, 121-136.
    [Google Scholar]
  11. Hanke, T., Samuel, R. V., Blanchard, T. J., Neumann, V. C., Allen, T. M., Boyson, J. E., Sharpe, S. A., Cook, N., Smith, G. L., Watkins, D. I., Cranage, M. P. & McMichael, A. J. ( 1999; ). 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]
  12. Hirsch, V. M., Fuerst, T. R., Sutter, G., Carroll, M. W., Yang, L. C., Goldstein, S., Piatak, M.Jr, Elkins, W. R., Alvord, W. G., Montefiori, D. C., Moss, B. & Lifson, J. D. ( 1996; ). Patterns of virus replication correlate with outcome in simian immunodeficiency virus (SIV)-infected macaques: effect of prior immunization with a trivalent SIV vaccine in modified vaccinia Ankara. Journal of Virology 70, 3741-3752.
    [Google Scholar]
  13. Hu, S.-L., Abrams, K., Barber, G. N., Moran, P., Zarling, J. M., Langlois, A. J., Kuller, L.-R., Morton, W. R. & Benveniste, R. E. ( 1992; ). Protection of macaques against SIV infection by subunit vaccines of SIV envelope glycoprotein gp160. Science 255, 456-459.[CrossRef]
    [Google Scholar]
  14. Kent, S. J., Stallard, V., Corey, L., Hu, S.-L., Morton, W. R., Gritz, L., Panicali, D. L. & Greenberg, P. D. ( 1994; ). Analysis of cytotoxic T lymphocyte responses to SIV proteins in SIV-infected macaques using antigen-specific stimulation with recombinant vaccinia and fowl poxvirus. AIDS Research and Human Retroviruses 10, 551-560.[CrossRef]
    [Google Scholar]
  15. Knapp, L. A., Lehman, E., Piekarczyk, M. S., Urvter, J. A. & Watkins, D. I. ( 1997; ). A high frequency of Mamu-A*01 in the rhesus macaque detected by PCR-SSP and direct sequencing. Tissue Antigens 50, 657-661.[CrossRef]
    [Google Scholar]
  16. Lehner, T., Wang, Y., Cranage, M., Bergmeier, L. A., Mitchell, E., Tao, L., Hall, G., Dennis, M., Cook, N., Brookes, R., Klavinskis, L., Jones, I., Doyle, C. & Ward, R. ( 1996; ). Protective mucosal immunity elicited by targeted iliac lymph node immunization with a subunit SIV envelope and core vaccine in macaques. Nature Medicine 2, 767-775.[CrossRef]
    [Google Scholar]
  17. Letvin, N. L. ( 1998; ). Progress in the development of an HIV-1 vaccine. Science 280, 1875-1880.[CrossRef]
    [Google Scholar]
  18. McMichael, A. J. & O’Callaghan, C. A. ( 1998; ). A new look at T cells. Journal of Experimental Medicine 187, 1367-1371.[CrossRef]
    [Google Scholar]
  19. Mayr, A., Hochstein-Mintzel, V. & Stickl, H. ( 1975; ). Abstammung Eigenschaften und Verwendug des attenuierten Vaccinia-Stammes MVA. Infection 105, 6-14.
    [Google Scholar]
  20. Meyer, H., Sutter, G. & Mayr, A. ( 1991; ). Mapping of deletions in the genome of the highly attenuated vaccinia virus MVA and their influence on virulence. Journal of General Virology 72, 1031-1038.[CrossRef]
    [Google Scholar]
  21. 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 Gag-specific cytotoxic T lymphocytes in SIVmac-infected rhesus monkeys. Journal of Immunology 147, 320-329.
    [Google Scholar]
  22. Miller, C., Alexander, N. J., Vogel, P., Anderson, J. & Marx, P. A. ( 1992; ). Mechanism of genital transmission of SIV: a hypothesis based on transmission studies and the location of SIV in the genital tract of chronically infected female rhesus macaques. Journal of Medical Primatology 21, 64-68.
    [Google Scholar]
  23. Moss, B. ( 1991; ). Vaccinia virus: a tool for research and vaccine development. Science 252, 1662-1667.[CrossRef]
    [Google Scholar]
  24. Ourmanov, I., Brown, C. R., Moss, B., Carroll, M., Wyatt, L., Pletneva, L., Goldstein, S., Venzon, D. & Hirsch, V. M. ( 2000; ). Comparative efficacy of recombinant modified vaccinia virus Ankara expressing simian immunodeficiency virus (SIV) gag–pol and/or env in macaques challenged with pathogenic SIV. Journal of Virology 74, 2740-2751.[CrossRef]
    [Google Scholar]
  25. Paoletti, E. ( 1996; ). Applications of poxvirus vectors to vaccination: an update. Proceedings of the National Academy of Sciences, USA 93, 11349-11353.[CrossRef]
    [Google Scholar]
  26. Polyanskaya, N., Bergmeier, L. A., Sharpe, S. A., Cook, N., Leech, S., Hall, G., Dennis, M., ten Haaft, P., Heeney, J., Manca, F., Lehner, T. & Cranage, M. P. ( 2001; ). Mucosal exposure to subinfectious doses of SIV primes gut-associated antibody secreting cells and T cells: lack of enhancement by nonneutralizing antibody. Virology 279, 527-538.[CrossRef]
    [Google Scholar]
  27. Ramirez, J. C., Gherardi, M. M., Rogriguez, D. & Estaban, M. ( 2000; ). Attenuated modified vaccinia virus Ankara can be used as an immunizing agent under conditions of preexisting immunity to the vector. Journal of Virology 74, 7651-7655.[CrossRef]
    [Google Scholar]
  28. Rooney, J. F., Wohlenberg, C., Cremer, K. J., Moss, B. & Notkins, A. L. ( 1988; ). Immunisation with a vaccinia virus recombinant expressing herpes simplex virus type 1 glycoprotein D: long-term protection and vaccine effect of vaccination. Journal of Virology 62, 1530-1534.
    [Google Scholar]
  29. Rud, E. W., Cranage, M., Yon, J., Quirk, J., Ogilvie, L., Cook, N., Webster, S., Dennis, M. & Clarke, B. E. ( 1994; ). Molecular and biological characterization of simian immunodeficiency virus macaque strain 32H proviral clones containing nef size variants. Journal of General Virology 75, 529-543.[CrossRef]
    [Google Scholar]
  30. Ruprecht, R. M. ( 1999; ). Live attenuated AIDS viruses as vaccines: promise or peril? Immunological Reviews 170, 135-149.[CrossRef]
    [Google Scholar]
  31. Seth, A., Ourmanov, I., Kuroda, M. J., Schmitz, J. E., Carroll, M. W., Wyatt, L. S., Moss, B., Forman, M. A., Hirsch, V. M. & Letvin, N. L. ( 1998; ). Recombinant modified vaccinia virus Ankara-simian immunodeficiency virus gag–pol elicits cytotoxic T lymphocytes in rhesus monkeys detected by a major histocompatibility complex class I/peptide tetramer. Proceedings of the National Academy of Sciences, USA 95, 10112-10116.[CrossRef]
    [Google Scholar]
  32. Seth, A., Ourmanov, I., Schmitz, J. E., Kuroda, M. J., Lifton, M. A., Nickerson, C. E., Wyatt, L., Carroll, M., Moss, B., Venzon, D., Letvin, N. L. & Hirsch, V. M. ( 2000; ). Immunization with a modified vaccinia virus expressing simian immunodeficiency virus (SIV) gag–pol primes for an anamnestic Gag-specific cytotoxic T-lymphocyte response and is associated with reduction of viremia after SIV challenge. Journal of Virology 74, 2502-2509.[CrossRef]
    [Google Scholar]
  33. Spira, A. L., Marx, P. A., Patterson, B. K., Mahoney, J., Koup, R. A., Wolinsky, S. M. & Ho, D. D. ( 1996; ). Cellular targets of infection and route of viral dissemination after an intravaginal inoculation of simian immunodeficiency virus into rhesus macaques. Journal of Experimental Medicine 183, 215-225.[CrossRef]
    [Google Scholar]
  34. Sutter, G. & Moss, B. ( 1992; ). Non-replicating vaccinia vector efficiently expresses recombinant genes. Proceedings of the National Academy of Sciences, USA 89, 10847-10851.[CrossRef]
    [Google Scholar]
  35. Sutter, G., Ohlmann, M. & Erfle, V. ( 1995; ). Non-replicating vaccinia vector efficiently expresses bacteriophage T7 R polymerase. FEBS Letters 371, 9-12.[CrossRef]
    [Google Scholar]
  36. Vogel, T., Norley, S., Beer, B. & Kurth, R. ( 1995; ). Rapid screening for Mamu A*01 positive rhesus macaques using a SIVmac Gag peptide-specific cytotoxic T-lymphocyte assay. Immunology 84, 482-487.
    [Google Scholar]
  37. Vogel, T. U., Fournier, J., Sherring, A., Ko, D., Parenteau, M., Bogdanovic, D., Mihowich, J. & Rud, E. W. ( 1998; ). Presence of circulating CTL induced by infection with wild-type or attenuated SIV and their correlation with protection from pathogenic SHIV challenge. Journal of Medical Primatology 27, 65-72.[CrossRef]
    [Google Scholar]
  38. Voss, G., Li, J., Manson, K., Wyand, M., Sodroski, J. & Letvin, N. L. ( 1995; ). Human Immunodeficiency virus type 1 envelope glycoprotein-specific cytotoxic T lymphocytes in simian-human immunodeficiency virus-infected rhesus monkeys. Virology 208, 770-775.[CrossRef]
    [Google Scholar]
  39. Wiktor, T. J., MacFarlan, R. I., Reagan, K. J., Dietzschold, B., Curtis, P. J., Wunner, W. H., Kieny, M.-P., Lathe, R., Lecocq, J.-P., Mackett, M., Moss, B. & Koprowski, H. ( 1984; ). Protection from rabies by a vaccinia virus containing the rabies virus glycoprotein gene. Proceedings of the National Academy of Sciences, USA 81, 7194-7198.[CrossRef]
    [Google Scholar]
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