Background:  Our laboratory is interested in defining cellular immune responses that control replication of highly pathogenic AIDS viruses. Recently we have defined the cellular immune responses in 2 rare cohorts that exhibit control over viral replication:  Elite controllers and successful vaccinees. Elite controllers effectively control HIV/ SIV replication and may facilitate definition of the attributes of a successful immune response. We have identified 6 macaques that have spontaneously controlled replication of the pathogenic AIDS virus SIV_mac239 for 1 to 5 years.  To determine which lymphocyte populations were responsible for this control, we transiently depleted their CD8⁺ T-cells in vivo. We have recently investigated whether vaccine-induced cellular immunity in the absence of any Env-specific antibodies can control viral replication following multiple low-dose challenges with the highly pathogenic SIV_mac239 isolate. We vaccinated 8 Mamu-A*01⁺ Indian rhesus macaques with SIV Gag, Tat, Rev, and Nef using a DNA prime adenovirus boost strategy. One year ago, these vaccines, along with 8 Mamu-A*01⁺ control macaques were challenged with repeated low dose SIV_mac239.

Conclusions:  The goal of an AIDS vaccine regimen designed to induce cellular immune responses should be to reduce viral set point and preserve memory CD4⁺ lymphocytes. I will present the rather surprising results of these depletion experiments and discuss their implications for HIV vaccine development. Furthermore, I will present the encouraging results from these studies that suggest that a vaccine designed to induce cellular immune responses might control HIV replication.