Matrix-M

Matrix-M is a vaccine adjuvant, a substance that is added to various vaccines to stimulate the immune response.^[1][2][3] It was patented in 2020 by Novavax^[4] and is composed of nanoparticles from saponins extracted from Quillaja saponaria (soapbark) trees, cholesterol, and phospholipids.^[5][6][7] It is an immune stimulating complex (ISCOM), which are nanospheres formed when saponin is mixed with two types of fats.^[8]

Composition

Matrix-M contains a complex mix of saponins extracted from the bark of soapbark trees (Quillaia) packaged into nanoparticles made of cholesterol and phospholipids. 15% of the nanoparticles are known as Matrix-C and contain saponins derived from "Fraction C" of the tree bark extract (mainly QS-21). Matrix-C has strong adjuvant activity but is also highly reactogenic (lethargy and lethality in mice). The remaining 85% are known as Matrix-A and contain "Fraction A" saponins. Matrix-A is a weaker adjuvant but is also very well tolerated. Combined, they form a strong adjuvant with acceptable reactogenecity.^[9]

Packaging saponins into nanoparticles achieves three things:^[9]

• Protection of the saponin molecule from hydrolysis
• Protection of tissue from direct saponin irritation (raw QS-21 causes immediate pain at injection site and also hemolysis in vitro)
• Targeted delivery of saponins to phagocytes

Forerunners to the Matrix-M technology include ISCOM (Morein et al., 1984) and ISCOMATRIX (CSL Limited, 2012).^[9]

Use

Adjuvants increase the body's immune response to a vaccine by creating higher levels of antibodies.^[10] They can either enhance, modulate, and/or prolong the body's immune response, reducing the number of vaccinations needed for immunization.^[11]

The Matrix-M adjuvant is used in a number of vaccine candidates, including the malaria vaccine R21/Matrix-M,^[1][12] influenza vaccines,^[2] and in the approved Novavax COVID-19 vaccine.^[5][13] In 2021, the R21/Matrix-M malaria vaccine candidate showed a 72% in sites with seasonal implementation and 67% in sites with age-based implementation in the modified per-protocol analysis. /> In influenza vaccine candidates, Matrix-M was shown to offer cross-protection against multiple strains of influenza.^[13][2][3]

Novavax is also testing a combined flu and COVID-19 vaccine candidate with Matrix-M.^[14]