University Hospital of Bordeaux and CNRS UMR 5234, Bordeaux, France.
University Hospital of Bordeaux and CNRS UMR 5164, Bordeaux, France.
PLoS One. 2014 Jun 25;9(6):e100452. doi: 10.1371/journal.pone.0100452. eCollection 2014.
In patients responding successfully to ART, the next therapeutic step is viral cure. An interesting strategy is antiviral vaccination, particularly involving CD8 T cell epitopes. However, attempts at vaccination are dependent on the immunogenetic background of individuals. The Provir/Latitude 45 project aims to investigate which CTL epitopes in proviral HIV-1 will be recognized by the immune system when HLA alleles are taken into consideration. A prior study (Papuchon et al, PLoS ONE 2013) showed that chronically-infected patients under successful ART exhibited variations of proviral CTL epitopes compared to a reference viral strain (HXB2) and that a generic vaccine may not be efficient. Here, we investigated viral and/or proviral CTL epitopes at different time points in recently infected individuals of the Canadian primary HIV infection cohort and assessed the affinity of these epitopes for HLA alleles during the study period. An analysis of the results confirms that it is not possible to fully predict which epitopes will be recognized by the HLA alleles of the patients if the reference sequences and epitopes are taken as the basis of simulation. Epitopes may be seen to vary in circulating RNA and proviral DNA. Despite this confirmation, the overall variability of the epitopes was low in these patients who are temporally close to primary infection.
在对 ART 治疗有反应的患者中，下一步的治疗策略是实现病毒治愈。一种有趣的策略是抗病毒疫苗接种，特别是涉及 CD8 T 细胞表位。然而，疫苗接种的尝试取决于个体的免疫遗传背景。Provir/Latitude 45 项目旨在研究在考虑 HLA 等位基因的情况下，前病毒 HIV-1 中的哪些 CTL 表位会被免疫系统识别。先前的一项研究（Papuchon 等人，PLoS ONE 2013）表明，在成功接受 ART 的慢性感染患者中，与参考病毒株（HXB2）相比，前病毒 CTL 表位存在变异，而通用疫苗可能效率不高。在这里，我们研究了加拿大原发性 HIV 感染队列中近期感染个体在不同时间点的病毒和/或前病毒 CTL 表位，并评估了这些表位在研究期间与 HLA 等位基因的亲和力。结果分析证实，如果以参考序列和表位为模拟基础，不可能完全预测哪些表位将被患者的 HLA 等位基因识别。表位可能在循环 RNA 和前病毒 DNA 中发生变异。尽管得到了这一确认，但在这些与原发性感染时间接近的患者中，表位的总体变异性较低。
