Innate immune receptors and antigen-presenting cells activated by Matrix-M2 adjuvant

Matrix-M2 is a proprietary saponin-based adjuvant system developed by Novavax, consisting of 40-nm honeycomb-like particles formed from Quillaja saponaria Molina saponins (Fraction-A and Fraction-C), cholesterol, and phospholipids (1, 2). Rather than targeting a single specific receptor, Matrix-M2 activates a broad range of innate immune receptors and antigen-presenting cells (APCs) to enhance vaccine immunogenicity. Its primary mechanism involves the recruitment of innate effector cells like neutrophils and monocytes to the injection site and the activation of the NLRP3 inflammasome within dendritic cells and macrophages (3, 4). This activation results in the release of key cytokines such as IL-1beta and IL-18, which facilitate the maturation of APCs and their migration to draining lymph nodes (2, 5). Consequently, Matrix-M2 promotes a potent and balanced immune response, characterized by high-titer neutralizing antibodies and strong Th1/Th2 cellular immunity (5, 6). It is a critical component of modern protein subunit vaccines, including those for COVID-19 (NVX-CoV2373) and malaria (R21/Matrix-M) (1, 6). Citations: (1) Magnusson et al. (2013) Vaccine; (2) Bengtsson et al. (2011) Expert Review of Vaccines; (3) Reimer et al. (2022) Frontiers in Immunology; (4) Novavax (2021) Matrix-M Technology Overview; (5) Keech et al. (2020) NEJM; (6) Datoo et al. (2021) The Lancet.

Other names

Matrix-M adjuvant targetsSaponin-based adjuvant receptorsMatrix-M2 activated immune pathwaysNLRP3 inflammasome (primary pathway)

Matrix-M2 acts by inducing a local immunocompetent environment at the injection site, promoting the rapid recruitment of neutrophils, monocytes, and dendritic cells. It triggers the activation of the NLRP3 inflammasome, leading to the secretion of pro-inflammatory cytokines (IL-1beta and IL-18) and enhancing the maturation and migration of antigen-presenting cells to draining lymph nodes for T-cell priming.