Vaccine-induced cytotoxic T lymphocytes protect against retroviral challenge

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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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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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Correspondence to Andreas Suhrbier.

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