Innate immune pattern-recognition and related systems activated by Matrix-M adjuvant

Matrix-M is a saponin-based adjuvant system composed of 40 nm honeycomb-like particles formed by Quillaja saponaria Molina saponins (Fraction-A and Fraction-C), cholesterol, and phospholipids (Bengtsson et al., 2011). Rather than targeting a single receptor, it triggers a broad array of innate immune pattern-recognition and related systems, leading to the rapid recruitment of various immune cells, including neutrophils, monocytes, and dendritic cells, to the injection site and draining lymph nodes (Magnusson et al., 2013). This activation results in the maturation of dendritic cells and the enhancement of antigen uptake and presentation, which significantly boosts the magnitude and quality of the immune response. Matrix-M is a key component of the Novavax COVID-19 vaccine (NVX-CoV2373), where it facilitates a robust and durable memory response against the SARS-CoV-2 spike protein (Keech et al., 2020). Its mechanism involves the induction of a local immunocompetent environment that supports both humoral and cellular (Th1/Th2) immunity without the need for direct TLR agonism, potentially involving the NLRP3 inflammasome pathway (Welsby et al., 2016). The adjuvant has also been successfully utilized in the R21 malaria vaccine, demonstrating its versatility in enhancing vaccine efficacy across different pathogens.

Other names

Matrix-M adjuvant systemSaponin-based adjuvant signalingMatrix-M1Matrix-M2

Matrix-M acts by inducing a local transient immunostimulatory environment, promoting the recruitment and activation of professional antigen-presenting cells (APCs) such as dendritic cells and macrophages to the injection site and draining lymph nodes (Magnusson et al., 2013). It enhances both Th1 and Th2 type immune responses and promotes high titers of neutralizing antibodies (Bengtsson et al., 2011).