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HIV vaccine candidate activation of hypoxia and the inflammasome in CD14+ monocytes is associated with a decreased risk of SIVmac251 acquisition.
Nature Medicine ( IF 82.9 ) Pub Date : 2018-Jun-01 , DOI: 10.1038/s41591-018-0025-7
Monica Vaccari 1 , Slim Fourati 2 , Shari N Gordon 1 , Dallas R Brown 1 , Massimilano Bissa 1 , Luca Schifanella 1 , Isabela Silva de Castro 1 , Melvin N Doster 1 , Veronica Galli 1 , Maria Omsland 1 , Dai Fujikawa 1 , Giacomo Gorini 1 , Namal P M Liyanage 1 , Hung V Trinh 3, 4 , Katherine M McKinnon 5 , Kathryn E Foulds 6 , Brandon F Keele 7 , Mario Roederer 6 , Richard A Koup 6 , Xiaoying Shen 8 , Georgia D Tomaras 8 , Marcus P Wong 9 , Karissa J Munoz 9 , Johannes S Gach 9 , Donald N Forthal 9 , David C Montefiori 10 , David J Venzon 11 , Barbara K Felber 12 , Margherita Rosati 13 , George N Pavlakis 13 , Mangala Rao 3 , Rafick-Pierre Sekaly 2 , Genoveffa Franchini 1
Affiliation  

Qualitative differences in the innate and adaptive responses elicited by different HIV vaccine candidates have not been thoroughly investigated. We tested the ability of the Aventis Pasteur live recombinant canarypox vector (ALVAC)-SIV, DNA-SIV and Ad26-SIV vaccine prime modalities together with two ALVAC-SIV + gp120 protein boosts to reduce the risk of SIVmac251 acquisition in rhesus macaques. We found that the DNA and ALVAC prime regimens were effective, but the Ad26 prime was not. The activation of hypoxia and the inflammasome in CD14+CD16- monocytes, gut-homing CCR5-negative CD4+ T helper 2 (TH2) cells and antibodies to variable region 2 correlated with a decreased risk of SIVmac251 acquisition. By contrast, signal transducer and activator of transcription 3 activation in CD16+ monocytes was associated with an increased risk of virus acquisition. The Ad26 prime regimen induced the accumulation of CX3CR1+CD163+ macrophages in lymph nodes and of long-lasting CD4+ TH17 cells in the gut and lungs. Our data indicate that the selective engagement of monocyte subsets following a vaccine prime influences long-term immunity, uncovering an unexpected association of CD14+ innate monocytes with a reduced risk of SIVmac251 acquisition.

中文翻译:

HIV 候选疫苗激活缺氧和 CD14+ 单核细胞中的炎症小体与 SIVmac251 获得风险降低相关。

不同候选艾滋病毒疫苗引起的先天反应和适应性反应的质量差异尚未得到彻底研究。我们测试了安万特巴斯德活重组金丝雀痘载体 (ALVAC)-SIV、DNA-SIV 和 Ad26-SIV 疫苗主要模式以及两种 ALVAC-SIV + gp120 蛋白增强剂降低恒河猴感染 SIV mac251 风险的能力我们发现 DNA 和 ALVAC prime 方案有效,但 Ad26 prime 无效。CD14 + CD16 -单核细胞、肠道归巢 CCR5 阴性 CD4 + T 辅助 2 ( TH 2) 细胞和可变区 2 抗体中缺氧和炎性体的激活与 SIV mac251感染风险降低相关。相比之下,CD16 +单核细胞中的信号转导器和转录激活剂 3 激活与病毒感染风险增加相关。Ad26 Prime 方案诱导淋巴结中 CX3CR1 + CD163 +巨噬细胞的积累以及肠道和肺部持久 CD4 + T H 17 细胞的积累。我们的数据表明,疫苗初免后单核细胞亚群的选择性参与会影响长期免疫力,揭示了 CD14 +先天单核细胞与 SIV mac251获得风险降低之间的意外关联。
更新日期:2018-05-22
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