Matrix-M adjuvant triggers inflammasome activation and enables antigen cross-presentation through induction of lysosomal membrane permeabilization
Behdad Zarnegar, Berit Carow, Jens Eriksson, Eva Spennare, Pontus Öhlund, Eray Akpinar, Emelie Bringeland, Ingrid Lekberg Osterman, Lena Lundqvist, Johanna Antti, Niklas Handin, Per-Henrik Helgesson, Johan Bankefors, Karin Lövgren Bengtsson, Mikael E. Sellin, Anna-Karin E. Palm, Linda Stertman, Carolina Lunderius Andersson
Abstract
Matrix-M ® adjuvant, containing saponins, delivers a potent adjuvant effect and good safety profile. Given that Matrix-M is composed of Matrix-A and Matrix-C particles, comprising different saponin fractions, understanding their distinct roles can provide deeper insight into the mechanism of action of Matrix-M and guide future applications. Here, we demonstrate that the antigen and Matrix-M, Matrix-A, or Matrix-C colocalize in lysosomes following uptake by bone marrow–derived dendritic cells. Matrix-M, Matrix-A, and Matrix-C induce lysosomal membrane permeabilization (LMP), but Matrix-C shows the highest LMP potential. LMP is required for interleukin (IL)-1β and IL-18 secretion in vitro. In vivo, a robust adjuvant effect of Matrix-M, Matrix-A, and Matrix-C is observed, both in the presence and absence of the NLRP3 inflammasome. LMP induced by Matrix-M, as well as Matrix-A and Matrix-C, also enables antigen cross-presentation. Thus, Matrix-induced LMP explains the capability of Matrix-M–adjuvanted protein vaccines to induce CD8 + T-cell responses.