Background:  Acute infection by simian immunodeficiency virus (SIV) causes a massive infection of CD4 memory cells throughout the body, leading directly to their destruction. Over the first few weeks after infection, as much as 80% of the CD4 memory compartment is destroyed; this represents a significant insult to the immune system.  Indeed, the extent of the destruction of the CD4 memory compartment during this early phase predicts long-term survival. Therefore, protecting against this destruction is an important goal for prophylactic intervention, such as vaccination.

Methods:  To test this, we vaccinated nonhuman primates with a variety of vectors encoding SIV genes; these regimens induced either cellular immune responses or cellular and humoral responses. 

Results:  Vaccines eliciting antigen-specific CD8 T-cell responses tempered the destruction of the CD4 memory compartment following challenge with SIV. The preservation of the memory compartment was evident at the early, post-acute time point (4 weeks), and persisted for many months. The extent of preservation was also highly inversely correlated with progression to death.

Conclusions:  These findings identify a key mechanism leading to differential rates of progression to AIDS in infected subjects. In addition, they point to the critical importance of reducing the cell-associated viral load during acute infection, through therapeutic or vaccination strategies. Finally, these studies show that a T-cell-based vaccine against HIV or SIV can have profound protective effects even in the absence of sterilizing immunity.