1887

Abstract

Convincing data on experimental vaccines against AIDS have been obtained in the simian immuno-deficiency virus (SIV) macaque model by preinfection with a virus attenuated by a deletion. To investigate the efficacy of a deletion mutant of SIVmac32H called pC8 as a live-attenuated vaccine after shorter preinfection periods and to learn more about the nature of the immune protection induced, eight rhesus monkeys were infected intravenously with the pC8 virus. All monkeys became persistently infected, exhibiting low cell-associated viral loads, but strong cellular and, in terms of binding antibodies, strong humoral antiviral responses. Two of eight pC8-infected monkeys developed an immuno-deficiency and were not challenged. Sequence analysis of their revealed complete replenishment of the deletion. The other six monkeys, two preinfected for 42 weeks and four for 22 weeks, were challenged with pathogenic spleen-derived SIV. Complete protection was achieved in four vaccinees. Virus was consistently detected in two vaccinees from the 22-week-group challenge, however, they remained clinically healthy over a prolonged period. Protection from challenge virus infection or a delayed disease development seemed to be associated with a sustained SIV-specific T helper cell response after challenge. Thus, a sterilizing immunity against superinfection with pathogenic SIV can be induced even after a relatively short waiting period of 22 weeks. Nevertheless, such a vaccine raises severe safety concerns because of its potential to revert to virulence.

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1996-12-01
2022-01-20
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References

  1. Ahmad S., Lohmann B., Marthas M., Giavedoni L., El-Ahmad Z., Haigwood N., Scandella C., Gardner M., Luciw P., Yilma T. 1994; Reduced virus load in rhesus macaques immunised with recombinant gp160 and challenged with simian immunodeficiency virus. AIDS Research and Human Retroviruses 10:195–204
    [Google Scholar]
  2. Almond N., Kent K., Cranage M., Rud E., Clarke B., Stott E. J. 1995; Protection by attenuated simian immunodeficiency virus in macaques against challenge with virus-infected cells. Lancet 345:1342–1344
    [Google Scholar]
  3. Baba T. W., Jeong Y. S., Penninck D., Bronson R., Greene M. F., Ruprecht R. M. 1995; Pathogenicity of live, attenuated SIV after mucosal infection of neonatal macaques. Science 267:1820–1825
    [Google Scholar]
  4. Bachmann B., Lüke W., Hunsmann G. 1992; Improvement of PCR amplified DNA sequencing with the aid of detergents. Nucleic Acids Research 18:1309
    [Google Scholar]
  5. Benveniste O., Vaslin B., Le Grand R., Cheret A., Matheux F., Theodora F., Cranage M. P., Dormont D. 1996; Comparative interleukin (IL)-2/interferon (IFN)-y and IL-4/IL-10 responses during acute infection of macaques inoculated with attenuated ne/-truncated or pathogenic SIVmac251 virus. Proceedings of the National Academy of Sciences, USA 93:3658–3663
    [Google Scholar]
  6. Cranage M. P., Cook N., Johnstone P., Greenaway P. J., Kitchin P. A., Stott E. J., Almond N., Baskerville A. 1990; SIV infection of rhesus macaques: in vitro titration of infectivity and development of an experimental vaccine. In Animal Models in AIDS pp 103–114 Edited by Schellekens H., Horzinek M. C. Amsterdam, Holland: Elsevier, Biomedical Press;
    [Google Scholar]
  7. Daniel M. D., Kirchoff F., Czajak S. C., Sehgal P. K., Desrosiers R. C. 1992; Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene. Science 258:1938–1941
    [Google Scholar]
  8. Desrosiers R. C., Wyand M. S., Kodama T., Ringler D. J., Arthur L. O., Segal P. K., Letvin N. L., King N. W., Daniel M. D. 1989; Vaccine protection against simian immunodeficiency virus infection. Proceedings of the National Academy of Sciences, USA 86:6353–6357
    [Google Scholar]
  9. Dittmer U., Lüke W., Stahl-Hennig C., Coulibaly C., Petry H., Bodemer H., Hunsmann G., Voss G. 1994; Early helper T-cell dysfunction in simian immunodeficiency virus but not in human immunodeficiency virus type-2-infected macaques. Journal of Medical Primatology 23:298–303
    [Google Scholar]
  10. Dittmer U., Stahl-Hennig C., Coulibaly C., Nisslein T., Lüke W., Fuchs D., Bodemer W., Petry H., Hunsmann G. 1995a; Repeated exposure of rhesus macaques to low doses of simian immunodeficiency virus (SIV) did not protect them against the consequences of a high-dose SIV challenge. Journal of General Virology 761307–1315
    [Google Scholar]
  11. Dittmer U., Nisslein T., Bodemer W., Petry H., Sauermann U., Stahl- Hennig C., Hunsmann G. 1995b; Cellular immune response of rhesus monkeys infected with a partially attenuated nef mutant of the simian immunodeficiency virus. Virology 212:392–397
    [Google Scholar]
  12. Fendrich C., Lüke W., Stahl-Hennig C., Herchenröder O., Fuchs D., Waehter H., Hunsmann G. 1989; Urinary neopterin concentrations in rhesus monkeys after infection with simian immunodeficiency virus strain 251. AIDS 3:305–307
    [Google Scholar]
  13. Franchini G., Robert-Guroff M., Tartaglia J., Aggarwal A., Abimiku A., Benson J., Markham P., Limbach K., Hurteau G., Fullen J., Aldrich K., Miller N., Sadoff J., Paoletti E., Gallo R. C. 1995; Highly attenuated HIV type 2 recombinant poxviruses, but not HIV-2 recombinant Salmonella vaccines, induce long-lasting protection in rhesus macaques. AIDS Research and Human Retroviruses 11:909–920
    [Google Scholar]
  14. Fuchs D., Hausen R., Reibnegger G., Werner E. R., Dierich M. P., Waehter H. 1988; Neopterin as a marker for activated cell-mediated immunity: application in HIV infection. Immunology Today 9:150–155
    [Google Scholar]
  15. Gallimore A., Cranage M., Cook N., Almond N., Bootman J., Rud E., Silvera P., Dennis M., Corcoran T., Stott J., McMichael A. McMichael F. 1995; Early suppression of SIV replication by CD8+ nef-specific cytotoxic T cells in vaccinated macaques. Nature Medicine 1:1167–1173
    [Google Scholar]
  16. Giavedoni L., Planelles V., Haighwood N., Ahmad S., Klug J., Marthas M., Gardner M., Luciw P., Yilma T. 1993; Immune response of rhesus macaques to recombinant SIV gp!30 does not protect from challenge infection. Journal of Virology 67:577–583
    [Google Scholar]
  17. Harada S., Purtilo D., Koyanagi Y., Sonnabend J., Yamamoto N. 1986; Sensitive assay for neutralising antibodies against AIDS-related viruses (HTLV-III/LAV). Journal of Immunological Methods 92:177–181
    [Google Scholar]
  18. Hasenkrug K. J., Brooks D. M., Nishio J., Chesebro B. 1996; Differing T-cell requirements for recombinant retrovirus vaccines. Journal of Virology 70:386–372
    [Google Scholar]
  19. Hoch J., Lang S. M., Weeger M., Stahl-Hennig C., Coulibaly C., Dittmer U., Hunsmann G., Fuchs D., Müller J., Sopper S., Fleckenstein B., Uberla K. 1995; vpr deletion mutant of simian immunodeficiency virus induces AIDS in rhesus monkeys. Journal of Virology 694807–4813
    [Google Scholar]
  20. Hu S. L., Abrams K., Barber G. N., Moran P., Zarling J. M., Langlois A. J., Kuller L., Mortan W. R., Benveniste R. E. 1992; Protection of macaques against SIV infection by subunit vaccines of SIV envelope glycoprotein gpl60. Science 255:456–459
    [Google Scholar]
  21. Israel Z. R., Edmonson P. F., Maul D. H., O’Neil S. P., Mossman S. P., Thiriart C., Farby L., Van Opstal O., Brack C., Bex F., Burny A., Fultz P. N., Mullins J. I., Hoover E. A. 1994; Incomplete protection, but suppression of virus burden, elicited by subunit simian immunodeficiency virus vaccines. Journal of Virology 68:1843–1853
    [Google Scholar]
  22. Joag S. V., Stephens E. B., Adams R. J., Foresman L., Narayan O. 1994; Pathogenesis of SIVmac infection in Chinese and Indian rhesus macaques: effects of splenectomy on virus burden. Virology 200:436–466
    [Google Scholar]
  23. Jurkiewicz E., Jansen R., Kunze B., Trowitzsch-Kienast W., Forche E., Reichenbach H., Hofle G., Hunsmann G. 1992; Three new potent HIV-1 inhibitors from myxobacteria. Antiviral Chemistry and Chemotherapy 3:189–193
    [Google Scholar]
  24. Kestler H. W., Ringler D. J., Mori K., Panicali D. L., Sehgal P., Daniel M. D., Desrosiers R. C. 1991; Importance of the nef gene for maintenance of high virus loads and for development of AIDS. Cell 65:651–662
    [Google Scholar]
  25. Lang S. M., Weeger M., Stahl-Hennig C., Coulibaly C., Hunsmann F., Muller J., Miiller-Hermelink H., Fuchs D., Waehter H., Daniel M. D., Desrosiers R. C., Fleckenstein B. 1993; Importance of vpr for infection of rhesus monkeys with simian immunodeficiency virus. Journal of Virology 67:902–912
    [Google Scholar]
  26. Lüke W., Voss G., Stahl-Hennig C., Coulibaly C., Petry H., Hunsmann G. 1993; Protection of cynomolgus macaques against infection by the human immunodeficiency virus type 2 strain ben (HIV- 2ben) through immunization with the virion-derived envelope glycoprotein gpl30. AIDS Research and Human Retroviruses 9:387–394
    [Google Scholar]
  27. Lüke W., Coulibaly C., Dittmer U., Voss G., Oesterle R., Makoschey A., Sauermann U., Jurkiewicz E., Stahl-Hennig C., Petry H., Hunsmann G. 1996; Simian immunodeficiency virus (SIV) gpl30 oligomers protect rhesus macaques (Macaca mulatto) against infection with SIVmac32H grown on T-cells or derived ex vivo . Virology 216:444–450
    [Google Scholar]
  28. Mills K., Page M., Chan L., Kitchin P., Stott J., Taffs F., Jones W., Rose J., Ling C., Silvera P., Corcoran T., Flanagan B., Burny A., Bex F., Delchambre M., Vanopstal O., Fabry L., Thirart C., Delers A., Dewilde M., Bruck C. 1992; Protection against SIV infection in macaques by immunization with inactivated virus from the BK28 molecular clone, but not with BK28-derived recombinant env and gag proteins. Journal of Medical Primatology 21:50–57
    [Google Scholar]
  29. Miyazawa M., Fujisawa R., Ishihara C., Takei Y. A., Shimizu T., Uenishi H., Yamagishi H., Kuribayashi K. 1995; Immunization with a single T helper cell epitope abrogates Friend virus-induced early erythroid proliferation and prevents late leukemia development. Journal of Immunology 155:748–758
    [Google Scholar]
  30. Murphy-Corb M., Martin L. N., Davison-Fairburn B., Montelaro R., Miller M., West M., Ohkawa S., Baskin G. B., Zhang J. Y., Putney S., Allison A. S., Eppstein D. 1989; A formalin-inactivated whole SIV vaccine confers protection in macaques. Science 246:1293–1297
    [Google Scholar]
  31. Norley S., Beer B., Binninger-Schinzel D., Cosma C., Kurth R. 1996; Protection from pathogenic SIVmac challenge following shortterm infection with a Nef-deficient attenuated virus. Virology 219:195–205
    [Google Scholar]
  32. Petry H., Dittmer U., Stahl-Hennig C., Coulibaly C., Makoschey B., Fuchs D., Wachter H., Tolle T., Morys-Wortman C., Kaup F. J., Jurkiewicz E., Liike W., Hunsmann G. 1995; Reactivation of human immunodeficiency virus type 2 in macaques after simian immunodeficiency virus SIVmac superinfection. Journal of Virology 69:5117–5123
    [Google Scholar]
  33. Rud E. W., Jon J. R., Larder B. A., Clarke B. E., Cook N., Cranage M. P. 1992; Infectious molecular clone of SIVmac32H: nef deletion controls ability to reisolate virus from rhesus macaques. In Vaccines 92 pp 229–235 Edited by Brown F., Chanock R. M., Ginsberg H. S., Lemer R. A. New York: Cold Spring Harbor Laboratory Press;
    [Google Scholar]
  34. Rud E. W., Cranage M., Yon J., Quirk J., Ogilvie L., Cook N., Webster S., Dennis M., Clarke B. E. 1994a; Molecular and biological characterization of simian immunodeficiency virus macaque strain 32H proviral clones containing size variants. Journal of General Virology 75529–543
    [Google Scholar]
  35. Rud E. W., Ogilvie L., Clarke B. E., Almond N., Kent K., Chan L., Page M., Kitchin P., Stott J., Cook N., Sharpe S., Ashworth T., Dennis M., Hall G., Cranage M. P. 1994b; A naturally attenuated SIVmac32H vaccine or viral interference. In Vaccines 94 pp 217–223 Edited by Norrby E., Brown F., Chanock R. M., Ginsberg H. S. New York: Cold Spring Harbor Laboratory Press;
    [Google Scholar]
  36. Shafferman A., Jahrling P. B., Benveniste R. E., Lewis M. G., Phipps T. J., Eden-McCutchan F., Sadoff J., Eddy G. A., Burke D. S. 1991; Protection of macaques with a simian immunodeficiency virus envelope peptide vaccine based on conserved human immunodeficiency virus type 1 sequences. Proceedings of the National Academy of Sciences, USA 88:7126–7130
    [Google Scholar]
  37. Stahl-Hennig C., Voss G., Nick S., Petry H., Fuchs D., Wachter H., Coulibaly C., Liike W., Hunsmann G. 1992; Immunization with Tween-ether-treated SIV adsorbed onto aluminium hydroxide protects monkeys against experimental SIV infection. Virology 186:588–596
    [Google Scholar]
  38. Stahl-Hennig C., Coulibaly C., Petry H., Voss G., Dittmer U., Bodemer W., Makoschey B., Jurkiewicz E., Lüke W., Hunsmann G. 1994; Immunization with virion-derived glycoprotein 130 from HIV- 2 or SIV protects macaques against challenge virus grown in human or simian cells or prepared ex vivo. AIDS Research and Human Retroviruses 10:S27–S32
    [Google Scholar]
  39. Sutjipto S., Pedersen N. C., Miller C. J., Gardner M. B., Hanson C. V., Gettie A., Jennings M., Higgins J., Marx P. A. 1990; Inactivated simian immunodeficiency virus vaccine failed to protect rhesus macaques from intravenous or genital mucosal infection but delayed disease in intravenously exposed animals. Journal of Virology 64:2290–2297
    [Google Scholar]
  40. Whatmore A. M., Cook N., Hall G. H., Sharpe S., Rud E. W., Cranage M. P. 1995; Repair and evolution of nef in vivo modulates simian immunodeficiency virus virulence. Journal of Virology 69:5117–5123
    [Google Scholar]
  41. Wyand M. S., Manson K. H., Garcia-Moll M., Montefiori D., Desrosiers R. C. 1996; Vaccine protection by a triple deletion mutant of simian immunodeficiency virus. Journal of Virology 70:3724–3733
    [Google Scholar]
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