Pole de Biologie, CHU de Bordeaux, 33076 Bordeaux, France.
CNRS UMR 5234, Université de Bordeaux, 33076 Bordeaux, France.
Viruses. 2020 Nov 5;12(11):1256. doi: 10.3390/v12111256.
We proposed a new HIV-1 therapeutic vaccine based on conserved cytotoxic T lymphocyte (CTL) epitopes of archived HIV-1 DNA according to their affinity to the dominant HLA-A and -B alleles of the population investigated. Our proposal (Hla Fitted VAC, HFVAC) was composed of 15 peptides originating from the RT, gag and nef parts of proviral DNA. Our aim was to investigate baseline immune reactivity to the vaccine in HIV-1 chronically infected patients at success of antiretroviral therapy (ART) who would be eligible for a therapeutic vaccine. Forty-one patients were tested. Most of them had been infected with HIV-1 subtype B and all had been receiving successful ART for 2 to 20 years. The predominant HLA-A and -B alleles were those of a Caucasian population. ELISPOT was carried out using the HFVAC peptides. In 22 patients, the PD-1 marker was investigated on CD4+ and CD8+ T cells by flow cytometry in order to evaluate global T cell exhaustion. ELISPOT positivity was 65% overall and 69% in patients exhibiting at least one HLA allele fitting with HFVAC. The percentages of CD4+ and CD8+ T cells expressing PD-1 were high (median values 23.70 and 32.60, respectively), but did not seem to be associated with an impairment of the immune response investigated in vitro. In conclusion, reactivity to HFVAC was high in this ART-treated population with dominant HLA alleles, despite potential cellular exhaustion associated with the PD-1 marker.
我们根据针对所研究人群中主要 HLA-A 和 -B 等位基因的亲和力，提出了一种基于 HIV-1 存档 DNA 保守细胞毒性 T 淋巴细胞（CTL）表位的新型 HIV-1 治疗性疫苗。我们的建议（Hla Fitted VAC，HFVAC）由源自 RT、gag 和 nef 部分的 15 个肽组成。我们的目的是研究在接受抗逆转录病毒治疗（ART）成功的慢性 HIV-1 感染患者中，对该疫苗的基线免疫反应性，这些患者将有资格接受治疗性疫苗。41 名患者接受了测试。他们中的大多数人感染了 HIV-1 亚型 B，并且所有人都接受了成功的 ART 治疗 2 至 20 年。主要的 HLA-A 和 -B 等位基因是白种人群的等位基因。使用 HFVAC 肽通过 ELISPOT 进行检测。在 22 名患者中，通过流式细胞术检测 CD4+和 CD8+T 细胞上的 PD-1 标志物，以评估整体 T 细胞耗竭情况。ELISPOT 阳性率总体为 65%，至少有一种与 HFVAC 匹配的 HLA 等位基因的患者阳性率为 69%。表达 PD-1 的 CD4+和 CD8+T 细胞的百分比较高（中位数分别为 23.70%和 32.60%），但似乎与体外研究的免疫反应受损无关。总之，在具有主要 HLA 等位基因的接受 ART 治疗的人群中，HFVAC 的反应性很高，尽管与 PD-1 标志物相关的细胞耗竭潜在存在。
