Zarnegar, B., et al. Matrix-M adjuvant triggers inflammasome activation and enables antigen cross-presentation through induction of lysosomal membrane permeabilization. NPJ Vaccines, 2025 Aug 5, 10(1):184.

Zarnegar, B., et al. Matrix-M adjuvant triggers inflammasome activation and enables antigen cross-presentation through induction of lysosomal membrane permeabilization. NPJ Vaccines, 2025 Aug 5, 10(1):184. PMID: 40764493

• This study investigates the cellular mechanisms underlying the adjuvant effects of Matrix-M, a saponin-based adjuvant used in licensed COVID-19 and malaria vaccines. 
• It demonstrates that Matrix-M and its constituent particles, Matrix-A and Matrix-C, are internalized by dendritic cells and localize within lysosomes, where they induce lysosomal membrane permeabilization (LMP). The study shows that all three particles, Matrix-A, Matrix-C, and Matrix-M, induce LMP, but Matrix-C and Matrix-M are particularly potent in this regard.
• The article discusses saponin fractions in detail. It explains that Matrix-M is composed of two distinct nanoparticles, Matrix-A and Matrix-C, which contain different saponin fractions, Fraction-A and Fraction-C, respectively. The study highlights that these saponin fractions, derived from Quillaja saponins, have distinct structural features, such as the presence or absence of fatty acyl chains, which influence their ability to induce lysosomal membrane permeabilization (LMP) and activate immune responses. Additionally, it notes that formulations containing specific saponin fractions, especially those with immunoactive properties like Fraction-C, are capable of promoting antigen cross-presentation and inflammasome activation, whereas crude saponin fractions lack this capacity.
• Matrix-M and its constituent particles, Matrix-A and Matrix-C, induce lysosomal membrane permeabilization (LMP) in dendritic cells, which is essential for activating innate immune responses such as IL-1β secretion and antigen cross-presentation. These effects contribute to the potent adjuvant activity of Matrix-M, enabling it to enhance both antibody production and T-cell responses independently of the NLRP3 inflammasome, thereby demonstrating its broad immunostimulatory capacity for effective vaccine formulations.

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