Developing a vaccine for human immunodeficiency virus (HIV) may be aided by a complete understanding of those rare cases in which some HIV-infected individuals control replication of the virus1,2,3. Most of these elite controllers express the histocompatibility alleles HLA-B*57 or HLA-B*27 (ref. 3). These alleles remain by far the most robust associations with low concentrations of plasma virus4,5, yet the mechanism of control in these individuals is not entirely clear. Here we vaccinate Indian rhesus macaques that express Mamu-B*08, an animal model for HLA-B*27-mediated elite control6, with three Mamu-B*08-restricted CD8+ T-cell epitopes, and demonstrate that these vaccinated animals control replication of the highly pathogenic clonal simian immunodeficiency virus (SIV) mac239 virus. High frequencies of CD8+ T cells against these Vif and Nef epitopes in the blood, lymph nodes and colon were associated with viral control. Moreover, the frequency of the CD8+ T-cell response against the Nef RL10 epitope (Nef amino acids 137–146) correlated significantly with reduced acute phase viraemia. Finally, two of the eight vaccinees lost control of viral replication in the chronic phase, concomitant with escape in all three targeted epitopes, further implicating these three CD8+ T-cell responses in the control of viral replication. Our findings indicate that narrowly targeted vaccine-induced virus-specific CD8+ T-cell responses can control replication of the AIDS virus.
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We would like to thank M. Stevenson, M. Reynolds, N. Maness and J. Sacha for discussions and suggestions. We also thank D. Evans, L. Heyer and Z. R. Bergman for facilitating the experiments. This work was funded in part by National Institutes of Health (NIH) grants R37 AI052056, RO1 AI076114, RR015371, contract number HHSN261200800001E and FAPERJ, INCTV, CNPq, MCT and FIOCRUZ.
D.B.A. has, anticipates, or has had financial interests with the Frontiers Foundation; Vivus, Inc: Kraft Foods; University of Wisconsin; University of Arizona; University of Miami; Paul, Weiss, Wharton & Garrison LLP; and Sage Publications.
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Mudd, P., Martins, M., Ericsen, A. et al. Vaccine-induced CD8+ T cells control AIDS virus replication. Nature 491, 129–133 (2012). https://doi.org/10.1038/nature11443
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