A proposed new paradigm for an anti-AIDS tolerogenic vaccine

C. Jacomet
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Abstract

Until now, despite 30 years of intensive work, the RV144 human immunodeficiency virus (HIV) vaccine trial initiated in 2003 remains so far the most protective vaccine prototype of all those tested (32% reduction in the infection rate three years after the vaccination) and the HIV epidemic is still spreading worldwide. In addition, antiretroviral therapy (ART) for people living with HIV is given for life as no other pharmacological intervention has allowed to maintain an undetectable viral load after ART withdrawal. Pr Andrieu and colleagues discovered tolerogenic CD8+T-cells that suppress simian immunodeficiency virus (SIV) specific activation, ensuing SIV reverse transcription suppression and viral replication-defective in Chinese macaques vaccinated by intragastric route with inactivated SIV particles + Lactobacillus rhamnosus. Moreover, in HIV-infected elite controllers with specific genetic features (HLA-1-Bw4-80i and KIR3DL1 genes), Pr Andrieu found out that similar tolerogenic CD8+T-cells suppress in the same manner HIV-specific activation, HIV reverse transcription, and HIV replication. These data justify the development of a tolerogenic vaccine composed of inactivated HIV particles + Lactobacillus rhamnosus that could be used as a preventive or therapeutic vaccine.
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一种抗艾滋病耐受原性疫苗的新模式
到目前为止,尽管经过了30年的密集工作,2003年开始的RV144人类免疫缺陷病毒(HIV)疫苗试验迄今仍是所有试验中最具保护性的疫苗原型(接种疫苗三年后感染率降低32%),艾滋病毒流行病仍在全世界蔓延。此外,对艾滋病毒感染者进行抗逆转录病毒治疗(ART)是终身的,因为没有其他药物干预可以在停药后维持无法检测到的病毒载量。Pr Andrieu及其同事发现,在中国猕猴经经SIV灭活颗粒+鼠李糖乳杆菌经腹腔接种后,耐受性CD8+ t细胞抑制SIV特异性激活,导致SIV逆转录抑制和病毒复制缺陷。此外,在HIV感染的具有特定遗传特征的精英控制者(HLA-1-Bw4-80i和KIR3DL1基因)中,Pr Andrieu发现相似的耐受性CD8+ t细胞以相同的方式抑制HIV特异性激活、HIV逆转录和HIV复制。这些数据证明开发一种由灭活的HIV颗粒+鼠李糖乳杆菌组成的耐受性原疫苗是合理的,这种疫苗可以用作预防性或治疗性疫苗。
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