Saponin-based adjuvants induce cross-presentation in dendritic cells by intracellular lipid body formation

Martijn H. den Brok, Christian Büll, Melissa Wassink, Annemarie M. de Graaf, Jori A. Wagenaars, Marthe Minderman, Mayank Thakur, Sebastian Amigorena, Eric O. Rijke, Carla C. Schrier and Gosse J. Adema ()
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Martijn H. den Brok: Radboud Institute for Molecular Life Sciences, Radboud UMC, Geert Grooteplein 26, 6525 GA
Christian Büll: Radboud Institute for Molecular Life Sciences, Radboud UMC, Geert Grooteplein 26, 6525 GA
Melissa Wassink: Radboud Institute for Molecular Life Sciences, Radboud UMC, Geert Grooteplein 26, 6525 GA
Annemarie M. de Graaf: Radboud Institute for Molecular Life Sciences, Radboud UMC, Geert Grooteplein 26, 6525 GA
Jori A. Wagenaars: Radboud Institute for Molecular Life Sciences, Radboud UMC, Geert Grooteplein 26, 6525 GA
Marthe Minderman: Radboud Institute for Molecular Life Sciences, Radboud UMC, Geert Grooteplein 26, 6525 GA
Mayank Thakur: Institute for Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Charité Universitätsmedizin, Augustenburger Platz 1, 13353
Sebastian Amigorena: INSERM, Institut Curie, Section Recherche, Rue d'Ulm 26, 75005
Eric O. Rijke: MSD Animal Health
Carla C. Schrier: MSD Animal Health
Gosse J. Adema: Radboud Institute for Molecular Life Sciences, Radboud UMC, Geert Grooteplein 26, 6525 GA

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13324

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