Abstract
Developing a vaccine for HIV may be aided by a complete understanding of those rare cases where some HIV-infected individuals control replication of the virus
1
–
3
. The majority of these elite controllers (ECs) express
HLA-B*57
or
HLA-B*27
3
. These alleles remain by far the most robust associations with low concentrations of plasma virus
4
,
5
, yet the mechanism of control in these individuals is not entirely clear. Here we vaccinated Indian rhesus macaques that express
Mamu-B*08
, an animal model for HLA-B*27
-
mediated elite control
6
, with three Mamu-B*08-restricted CD8
+
T cell epitopes and demonstrate that these vaccinated animals controlled replication of the highly pathogenic SIVmac239 clonal virus. High frequencies of CD8
+
T cells against these Vif and Nef epitopes in the blood, lymph nodes and colon, were associated with viral control. Moreover, the frequency of the Nef RL10-specific response correlated significantly with reduced acute phase viremia. Finally, two of the eight vaccinees lost control of viral replication in the chronic phase, concomitant with escape in all three targeted epitopes, further implicating these three CD8
+
T cell responses in control of viral replication. Our findings indicate that narrowly targeted vaccine-induced virus-specific CD8
+
T cell responses can control replication of the AIDS virus.
