Gene expression profiling of rhesus macaques vaccinated with ALVAC-SIVgpe DNA + SIVgp120 protein subunit and unvaccinated controls after challenge with SIVmac251 - 11 wks post-infection. Macaca mulatta

The SIVmac251 macaque model has been used to evaluate the efficacy of vaccine for HIV. Exposure of macaques to a single high dose of SIVmac251 results in transmission of multiple viral variants, which contrasts the few HIV variants typically transmitted in humans. In here, we investigated whether the dose of SIVmac251 challenge affected vaccination efficacy and found that exposure of the immunized macaques to single high dose of SIVmac251 resulted in no vaccine efficacy, whereas exposure to a tenfold lower dose resulted in protection from SIVmac251 acquisition and protection from disease in animals that become infected. The dose of challenge did not affect the expression of inflammatory genes in the gut in acute infection, but at set point, a significant down regulation of interferon responsive genes and up regulation of genes involved in B and T-cell responses, was observed only in vaccinated animals exposed to a lower dose of SIVmac251. Accordingly, in these animals, we also found a significant correlation with vaccine induced T-cell responses and protection from disease. These data demonstrate that the evaluation of the efficacy of vaccine candidates for HIV relies on accurate modeling in macaques to better mimic HIV transmission to humans. Overall design: A total of 34 RNA samples were hybridized on to Rhesus Affymetrix 3' Expression arrays. The study was composed of 9 vaccinated and 9 control animals subjected to a low dose challenge and 7 vaccinated and 9 control animals subjected to a high dose challenge

SIVmac251猕猴模型已被用于评估HIV疫苗的保护效力。猕猴单次暴露于高剂量SIVmac251后，会感染多种病毒变体，这与人类中通常仅传播少数HIV变体的情况形成鲜明对比。本研究旨在探究SIVmac251攻毒剂量是否会影响疫苗效力，结果发现：免疫后的猕猴暴露于单次高剂量SIVmac251时未表现出疫苗保护效力，而暴露于低10倍剂量时，则可防止SIVmac251感染，且对已感染动物的疾病进展具有保护作用。攻毒剂量并未影响急性感染阶段肠道炎症基因的表达，但在感染稳态期，仅在接种疫苗且暴露于低剂量SIVmac251的动物中，观察到干扰素应答基因的显著下调，以及参与B细胞和T细胞应答的基因的显著上调。此外，在这类动物中，我们还发现疫苗诱导的T细胞应答与疾病保护之间存在显著相关性。上述数据表明，评估HIV候选疫苗的效力需依托猕猴模型进行精准建模，以更好地模拟人类HIV的传播过程。实验整体设计：共计34份RNA样本在恒河猴Affymetrix 3'表达芯片上完成杂交。本研究共分为四组：9只免疫猕猴与9只对照猕猴接受低剂量攻毒，另有7只免疫猕猴与9只对照猕猴接受高剂量攻毒。