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Vaccine-induced cytotoxic T lymphocytes protect against retroviral challenge

Abstract

The development of prophylactic vaccines against retroviral diseases has been impeded by the lack of obvious immune correlates for protection 1, 2 . Cytotoxic T-lymphocyte (CTL) 3, 4 , CD4-lymphocyte 5 , chemokine 6 and/or antibody responses 7 have all been associated with protection against HIV and AIDS; however, effective and safe vaccination strategies remain elusive 1, 8 . Here we show that vaccination with a minimal ovine CTL peptide epitope identified within gp51 of the retrovirus bovine leukemia virus (BLV), consistently induced peptide-specific CTLs. Only sheep whose CTLs were also capable of recognizing retrovirus-infected cells were fully protected when challenged with BLV. This retrovirus displays limited sequence variation 9 ; thus, in the relative absence of confounding CTL escape variants 10 , virus-specific CTLs targeting a single epitope were able to prevent the establishment of a latent retroviral infection.

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Figure 1: a, Env is a target of BLV-specific CTLs.
Figure 2: The minimal CTL epitope recognized by env-specific CTLs is ISIDQILEA.
Figure 3: CTL responses after peptide immunization.
Figure 4: Sheep with BLV-specific CTLs were protected against retroviral challenge.

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References

  1. Burton, D.R. & Moore, J.P. Why do we not have an HIV vaccine and how can we make one? Nature Med. S4, 495–498 (1998).

    Article  Google Scholar 

  2. de The, G. & Kazanji, M.J. An HTLV-I/II vaccine: from animal models to clinical trials? Acquir. Immune Defic. Syndr. Hum. Retrovirol. 13, S191–S198 ( 1996).

    Article  CAS  Google Scholar 

  3. Rowland-Jones, S., Tan, R. & McMichael, A. Role of cellular immunity in protection against HIV infection. Adv. Immunol. 65, 277– 346 (1997).

    Article  CAS  Google Scholar 

  4. Gallimore, A. et al. Early suppression of SIV replication by CD8+ nef-specific cytotoxic T cells in vaccinated macaques. Nature Med. 1, 1167–1173 (1995).

    Article  CAS  Google Scholar 

  5. Rosenberg, E.S. et al. Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science 278, 1447 –1450 (1997).

    Article  CAS  Google Scholar 

  6. Garzino-Demo, A., Devico, A.L. & Gallo, R.C. Chemokine receptors and chemokines in HIV infection. J. Clin. Immunol. 18, 243– 255 (1998).

    Article  CAS  Google Scholar 

  7. Burton, D.R. A vaccine for HIV type 1: the antibody perspective. Proc. Natl. Acad. Sci. USA 94, 10018–10023 (1997).

    Article  CAS  Google Scholar 

  8. Yasutomi, Y. et al. A vaccine-elicited, single viral epitope-specific cytotoxic T lymphocyte response does not protect against intravenous, cell-free simian immunodeficiency virus challenge. J. Virol. 69, 2279–2284 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Kettmann, R.A. et al. in The Retroviridae Vol. 3 (ed. Levy, J.A.) 39–81 (Plenum, New York, 1994).

    Book  Google Scholar 

  10. Mortara, L. et al. Selection of virus variants and emergence of virus escape mutants after immunization with an epitope vaccine. J. Virol. 72, 1403–1410 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. McClure, S.J., Davey, R.J., Lloyd, J.B. & Emery, D.L. Depletion of IFN-gamma, CD8+ or TCR gamma delta+ cells in vivo during primary infection with an enteric parasite (Trichostrongylus colubriformis) enhances protective immunity. Immunol. Cell Biol. 73, 552– 555 (1995).

    Article  CAS  Google Scholar 

  12. Gatei, M.H. et al. Protection of sheep against bovine leukemia virus (BLV) infection by vaccination with recombinant vaccinia viruses expressing BLV envelope glycoproteins: correlation of protection with CD4 T-cell response to gp51 peptide 51-70. J. Virol. 67, 1803–1810 (1993).

  13. Scalzo, A.A. et al. Induction of protective cytotoxic T cells to murine cytomegalovirus by using a nonapeptide and a human-compatible adjuvant (Montanide ISA 720). J. Virol. 69, 1306–1309 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Mammerickx, M., Palm, R., Portetelle, D. & Burny, A. Experimental transmission of enzootic bovine leukosis to sheep: latency period of the tumoral disease. Leukemia 2, 103–107 (1988).

    CAS  PubMed  Google Scholar 

  15. Kent, S.J., Hu, S.L., Corey, L., Morton, W.R. & Greenberg, P.D. Detection of simian immunodeficiency virus (SIV)-specific CD8+ T cells in macaques protected from SIV challenge by prior SIV subunit vaccination. J. Virol. 70, 4941– 4947 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Collins, K.L., Chen, B.K., Kalams, S.A., Walker, B.D. & Baltimore, D. HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes. Nature 391, 397–401 (1998).

    Article  CAS  Google Scholar 

  17. Dalgleish, A.G. Human T-cell lymphotropic virus type 1: infections and pathogenesis. Curr. Opin. Infect. Dis. 11, 195–199 (1998).

    Article  CAS  Google Scholar 

  18. Thomson, S.A. et al. Delivery of multiple CD8 cytotoxic T cell epitopes by DNA vaccination. J. Immunol. 160, 1717– 1723 (1998).

    CAS  PubMed  Google Scholar 

  19. Andrew, M. et al. Antigen specificity of the ovine cytotoxic T lymphocyte response to bluetongue virus. Vet. Immunol. Immunopathol. 47 , 311–322 (1995).

    Article  CAS  Google Scholar 

  20. Coulston, J. et al. Molecular cloning and sequencing of an Australian isolate of proviral bovine leukaemia virus DNA: Comparison with other isolates. J. Gen. Virol. 71, 1737–1746 (1990).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank R. Verrall and B. Shirley (School of Veterinary Science and Animal Production, University of Queensland) for care of the animals in this study. This work was supported by the Cooperative Research Centre for Vaccine Technology, the Australian Commonwealth AIDS Research Grants Program and Related Diseases, and the Australian Centre for International & Tropical Health & Nutrition.

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Hislop, A., Good, M., Mateo, L. et al. Vaccine-induced cytotoxic T lymphocytes protect against retroviral challenge . Nat Med 4, 1193–1196 (1998). https://doi.org/10.1038/2690

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