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Abstract
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.