Emulsion-based adjuvants have been demonstrated to be an effective tool in increasing vaccine efficacy. Here, we aimed to launch a mechanistic study on how emulsion adjuvants interact with immune cells and to elucidate the roles of the core oil in vaccine immunogenicity. Our results showed that treatment of dendritic cells (DCs) and splenocytes with a squalene-based emulsion (referred as SqE) induced reactive oxidative species (ROS) production and resulted in an increase in apoptotic and necrotic cells in a concentration- and time-dependent manner. Furthermore, DCs cocultured with cellular debris of SqE-pretreated splenocytes resulted in a higher level of ovalbumin (OVA) antigen uptake by DCs than those cocultured with untreated splenocytes. Interestingly, the potency was rather attenuated when splenocytes were pretreated with N-acetyl-cysteine, an antioxidant. Notably, SqE possesses a high impact on eliciting ROS-mediated antigen uptake compared with a squalane-based emulsion (SqA). Concordantly, immunogenicity studies have shown that SqE is better able than SqA to activate antigen-presenting cells, and to enhance antigen-specific T-cell immunity. Taken together, our results show that unsaturated squalene oil cored within emulsions plays a crucial role in ROS-mediated antigen uptake and cellular immunity, providing a basis for the design and development of vaccine adjuvant.

中文翻译：

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乳液疫苗佐剂中的不饱和角鲨烯含量在ROS介导的抗原摄取和细胞免疫中起着至关重要的作用

已经证明基于乳液的佐剂是提高疫苗效力的有效工具。在这里，我们旨在开展一项关于乳剂佐剂如何与免疫细胞相互作用的机制研究，并阐明核心油在疫苗免疫原性中的作用。我们的结果表明，以角鲨烯基乳剂（称为SqE）处理树突状细胞（DC）和脾细胞会诱导活性氧化物质（ROS）的产生，并导致凋亡和坏死细胞的浓度和时间依赖性增加方式。此外，与经SqE预处理的脾细胞的细胞碎片共培养的DC比与未经处理的脾细胞共培养的DC摄取更高水平的卵清蛋白（OVA）抗原。有趣的是，当用N-乙酰半胱氨酸，抗氧化剂。值得注意的是，与基于角鲨烷的乳剂（SqA）相比，SqE对引起ROS介导的抗原摄取具有很高的影响。相应地，免疫原性研究表明，SqE比SqA更能激活抗原呈递细胞，并增强抗原特异性T细胞免疫。两者合计，我们的研究结果表明，乳液中核心的不饱和角鲨烯油在ROS介导的抗原摄取和细胞免疫中起着至关重要的作用，为疫苗佐剂的设计和开发提供了基础。