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<p>Matrix-M<sup>®</sup> 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<sup>+</sup> T-cell responses.</p>

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Matrix-M adjuvant triggers inflammasome activation and enables antigen cross-presentation through induction of lysosomal membrane permeabilization

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月5日

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  • 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

摘要

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.