International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
AIDS. 2010 Nov 27;24(18):2777-87. doi: 10.1097/QAD.0b013e3283402206.
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.
在我们之前关于预防性 T 细胞疫苗的研究中，一些接种疫苗的猕猴控制了猴免疫缺陷病毒 (SIV) 的挑战。这些动物在急性期允许病毒血症，但在设定点后表现出持续的病毒控制。在这里，我们研究了这些 SIV 控制器在挑战后病毒特异性细胞免疫反应的广度。
我们之前报告说，在一群具有 MHC 单倍型 90-120-Ia 的缅甸猕猴中，用表达 Gag 的疫苗免疫可导致对 SIVmac239 的挑战产生非无菌控制，但不能对携带多个细胞毒性 T 淋巴细胞 (CTL) 逃逸 gag 突变的突变 SIV 产生非无菌控制。在本研究中，我们研究了在那些维持野生型 SIVmac239 控制的疫苗接种者中，在挑战后是否会诱导针对突变 SIV 复制的更广泛的细胞免疫反应。
我们分析了这些 SIV 控制器（n = 8）的细胞免疫反应。
这些控制器在慢性期产生了针对 SIV 非 Gag 抗原以及 Gag 的 CTL 反应。接种疫苗后，从这些动物获得的 CD8(+) 细胞在体外抑制野生型 SIV 复制，但对突变 SIV 复制大多没有抑制作用，而在挑战后的慢性期 CD8(+) 细胞则显示出有效的抗突变 SIV 功效。CD8(+) 细胞在体外抗突变 SIV 功效的水平与 Vif 特异性 CD8(+) T 细胞频率相关。在慢性期，即使在突变 SIV 超挑战后，血浆病毒血症也保持不可检测。
这些结果表明，基于疫苗的野生型 SIV 控制器可以获得具有抑制携带 CTL 逃逸突变的 SIV 变异体复制潜力的 CD8(+) 细胞。
