Matrix-M adjuvant-activated innate immune receptors (Matrix-M receptors)

Matrix-M is a potent saponin-based adjuvant system composed of 40-nm nanoparticles that incorporate purified saponin fractions from the Quillaja saponaria tree, cholesterol, and phospholipids [1, 12]. It functions by activating the innate immune system, specifically targeting antigen-presenting cells (APCs) like dendritic cells and macrophages to enhance the magnitude and quality of the adaptive immune response [1, 10]. The primary mechanism involves the induction of lysosomal membrane permeabilization (LMP), which triggers the NLRP3 inflammasome and facilitates the cross-presentation of antigens to CD8+ T cells [2, 11, 13]. This results in a balanced Th1/Th2 response and the generation of high-titer, long-lasting antibodies and cellular immunity [1, 14]. Matrix-M is a key component of the Novavax COVID-19 vaccine (Nuvaxovid) and the R21/Matrix-M malaria vaccine, demonstrating its clinical utility in providing protection against major global pathogens [7, 10]. Its ability to promote robust T-cell responses also makes it a promising candidate for therapeutic cancer vaccines [13].

Other names

Saponin-based adjuvant receptorsNLRP3 inflammasomePattern recognition receptors (PRRs)Innate immune sensors

Matrix-M induces lysosomal membrane permeabilization (LMP) in antigen-presenting cells, leading to the activation of the NLRP3 inflammasome and the release of pro-inflammatory cytokines like IL-1β and IL-18 [2, 11]. It also facilitates the escape of antigens from the endosome into the cytosol, promoting cross-presentation on MHC class I molecules and the subsequent activation of CD8+ T cells [13].