Abstract
Saponin-based adjuvants (SBAs) are being used in animal and human (cancer) vaccines, as they induce protective cellular immunity. Their adjuvant potency is a factor of inflammasome activation and enhanced antigen cross-presentation by dendritic cells (DCs), but how antigen cross-presentation is induced is not clear. Here we show that SBAs uniquely induce intracellular lipid bodies (LBs) in the CD11b+ DC subset in vitro and in vivo. Using genetic and pharmacological interference in models for vaccination and in situ tumour ablation, we demonstrate that LB induction is causally related to the saponin-dependent increase in cross-presentation and T-cell activation. These findings link adjuvant activity to LB formation, aid the application of SBAs as a cancer vaccine component, and will stimulate development of new adjuvants enhancing T-cell-mediated immunity.
Highlights
Saponin-based adjuvants (SBAs) are being used in animal and human vaccines, as they induce protective cellular immunity
dendritic cells (DCs) can be classified as conventional DCs, plasmacytoid DCs or monocyte-derived DCs20. cDCs are located in lymphoid and non-lymphoid tissues and can be further classified into two ontogenetically distinct subtypes: the CD8a þ /CD103 þ DCs and the CD11b þ DCs21,22
By testing a panel of classical non-microbial vaccine adjuvants, we first confirmed that the saponin containing immune stimulatory complexes (ISCOMs) Matrix C induced a dramatic increase in ovalbumin (OVA) antigen cross-presentation in GM-CSF-propagated DCs (Fig. 1c; Supplementary Fig. 1a)
Summary
Saponin-based adjuvants (SBAs) are being used in animal and human (cancer) vaccines, as they induce protective cellular immunity. Using genetic and pharmacological interference in models for vaccination and in situ tumour ablation, we demonstrate that LB induction is causally related to the saponin-dependent increase in cross-presentation and T-cell activation. These findings link adjuvant activity to LB formation, aid the application of SBAs as a cancer vaccine component, and will stimulate development of new adjuvants enhancing T-cell-mediated immunity. Dendritic cells (DCs) have a critical role in the in vivo effectiveness of SBA-aided vaccines, and enhanced antigen cross-presentation by DCs has been reported to be important for the ability of SBAs to induce cellular CD8 þ T-cell immunity[17]. SBAs trigger an unprecedented level of cross-presentation[11], but how SBAs steer this process is unknown
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