Broadening of CD8+ cell responses in vaccine-based simian immunodeficiency virus controllers

Abstract

In our prior study on a prophylactic T-cell-based vaccine, some vaccinated macaques controlled a simian immunodeficiency virus (SIV) challenge. These animals allowed viremia in the acute phase but showed persistent viral control after the setpoint. Here, we examined the breadth of postchallenge virus-specific cellular immune responses in these SIV controllers. We previously reported that in a group of Burmese rhesus macaques possessing the MHC haplotype 90-120-Ia, immunization with a Gag-expressing vaccine results in nonsterile control of a challenge with SIVmac239 but not a mutant SIV carrying multiple cytotoxic T lymphocyte (CTL) escape gag mutations. In the present study, we investigated whether broader cellular immune responses effective against the mutant SIV replication are induced after challenge in those vaccinees that maintained wild-type SIVmac239 control. We analyzed cellular immune responses in these SIV controllers (n = 8). These controllers elicited CTL responses directed against SIV non-Gag antigens as well as Gag in the chronic phase. Postvaccinated, prechallenge CD8(+) cells obtained from these animals suppressed wild-type SIV replication in vitro, but mostly had no suppressive effect on the mutant SIV replication, whereas CD8(+) cells in the chronic phase after challenge showed efficient antimutant SIV efficacy. The levels of in-vitro antimutant SIV efficacy of CD8(+) cells correlated with Vif-specific CD8(+) T-cell frequencies. Plasma viremia was kept undetectable even after the mutant SIV superchallenge in the chronic phase. These results suggest that vaccine-based wild-type SIV controllers can acquire CD8(+) cells with the potential to suppress replication of SIV variants carrying CTL escape mutations.