Matrix-M adjuvant triggers inflammasome activation and enables antigen cross-presentation through induction of lysosomal membrane permeabilization.
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Zarnegar B, Carow B, Eriksson J, Spennare E, Öhlund P, Akpinar E, Bringeland E, Osterman IL, Lundqvist L, Antti J, Handin N, Helgesson PH, Bankefors J, Lövgren Bengtsson K, Sellin ME, Palm AE, Stertman L, Lunderius Andersson C
NPJ Vaccines 10 (1) 184 [2025-08-05; online 2025-08-05]
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.
PubMed 40764493
DOI 10.1038/s41541-025-01243-5
Crossref 10.1038/s41541-025-01243-5
pmc: PMC12325594
pii: 10.1038/s41541-025-01243-5