Control of HIV-1 replication following nonsterilizing HIV-1 vaccination could be achieved by vaccine-elicited CD8؉ T-cell-mediated antiviral activity. To date, neither the functional nor the phenotypic profiles of CD8 ؉ T cells capable of this activity are clearly understood; consequently, little is known regarding the ability of vaccine strategies to elicit them. We used multiparameter flow cytometry and viable cell sorts from phenotypically defined CD8؉ T-cell subsets in combination with a highly standardized virus inhibition assay to evaluate CD8 ؉ T-cell-mediated inhibition of viral replication. Here we show that vaccination against HIV-1 Env and Gag-Pol by DNA priming followed by recombinant adenovirus type 5 (rAd5) boosting elicited CD8 ؉ T-cell-mediated antiviral activity against several viruses with either lab-adapted or transmitted virus envelopes. As it did for chronically infected virus controllers, this activity correlated with HIV-1-specific CD107a or macrophage inflammatory protein 1␤ (MIP-1␤) expression from HIV-1-specific T cells. Moreover, for vaccinees or virus controllers, purified memory CD8؉ T cells from a wide range of differentiation stages were capable of significantly inhibiting virus replication. Our data define attributes of an antiviral CD8 ؉ T-cell response that may be optimized in the search for an efficacious HIV-1 vaccine.

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