Elite controllers are rare individuals who are infected with HIV-1 yet maintain low to undetectable levels of virus in their blood and have no disease. Many of these people express specific major histocompatibility complex (MHC) class I alleles, which suggests that viral control is mediated by CD8+ T cells. David Watkins and his colleagues now report that in a monkey model of elite control of simian immunodeficiency virus (SIV) infection, CD8+ T cells targeting just three epitopes in the SIV Vif and Nef proteins correlate with control of virus replication (Nature doi:10.1038/nature11443).

In these authors' model of elite control—rhesus macaques expressing the MHC class I molecule Mamu-B*08 and infected with a highly pathogenic SIV—Mamu-B*08–restricted CD8+ T cells recognizing three SIV epitopes (two in Vif and one in Nef) have been shown to predominate the T cell response. Watkins and his colleagues have now assessed the importance of these CD8+ T cell responses by vaccinating Mamu-B*08+ macaques with vectors encoding or not encoding the three immunodominant SIV epitopes and subsequently challenging the macaques intrarectally with high doses of pathogenic SIVmac239. They found that all macaques vaccinated with the immunodominant T cell epitopes robustly controlled virus early in infection and showed higher post-infection T cell responses specific for two of the epitopes, Vif RL9 and Nef Rl10, than the macaques vaccinated with nonimmunodominant SIV epitopes. In particular, cytotoxic T cells recognizing Nef RL10 were associated with viral control during the chronic phase of infection. A surge in viremia in two macaques vaccinated with the immunodominant epitopes during chronic phase was associated with escape of the immunodominant epitopes, further underlining their importance in T cell maintenance of viral control. This study will encourage further investigation of the relevant mechanisms and increase the potential for targeted vaccines to induce CD8+ T cell mediated control of HIV infection.