All HIV vaccine efficacy trials to date have ended in failure. Structural features of the Envelope glycoprotein and its enormous variability have frustrated efforts to induce broadly reactive neutralizing antibodies. Existing T cell-based vaccines have shown only limited ability to control virus replication in the acute phase of infection in preclinical challenge models. To explore the extent to which vaccine-induced cellular immune responses, in the absence of neutralizing antibodies, can control replication of an AIDS virus, we vaccinated 8 macaques with a DNA/Ad5 regimen expressing all of the proteins of SIV_mac239 except Envelope. Vaccinees mounted high-frequency T cell responses against 11-34 epitopes in the vaccine. We have now challenged the vaccinees and 8 naïve control animals with repeated low doses of the heterologous biological isolate SIV_smE660. I will discuss the results of this experiment.