Chemistry:Matrix-M

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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]

References

  1. ↑ 1.0 1.1 Datoo, Mehreen S.; Natama, Magloire H.; Somé, Athanase; Traoré, Ousmane; Rouamba, Toussaint; Bellamy, Duncan; Yameogo, Prisca; Valia, Daniel et al. (2021-05-15). "Efficacy of a low-dose candidate malaria vaccine, R21 in adjuvant Matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial" (in English). The Lancet 397 (10287): 1809–1818. doi:10.1016/S0140-6736(21)00943-0. ISSN 0140-6736. PMID 33964223. 
  2. ↑ 2.0 2.1 2.2 Magnusson, Sofia E.; Reimer, Jenny M.; Karlsson, Karin H.; Lilja, Lena; Bengtsson, Karin Lövgren; Stertman, Linda (2013-03-25). "Immune enhancing properties of the novel Matrix-M adjuvant leads to potentiated immune responses to an influenza vaccine in mice" (in en). Vaccine 31 (13): 1725–1733. doi:10.1016/j.vaccine.2013.01.039. ISSN 0264-410X. PMID 23384754. https://www.sciencedirect.com/science/article/pii/S0264410X13001072. 
  3. ↑ 3.0 3.1 "NanoFlu is on the FDA's Vaccine Fast-Track" (in en-US). https://www.precisionvaccinations.com/novavax-nanoflu-recombinant-quadrivalent-seasonal-influenza-vaccine. 
  4. ↑ "US Patent for Highly efficient influenza matrix (M1) proteins Patent (Patent # 10,544,399 issued January 28, 2020) - Justia Patents Search". https://patents.justia.com/patent/10544399. 
  5. ↑ 5.0 5.1 Satyanarayana, Megha (2021-08-17). "A new, powerful malaria vaccine may be on the horizon". https://cen.acs.org/pharmaceuticals/vaccines/new-powerful-malaria-vaccine-horizon/99/i31. 
  6. ↑ "Is Old Vaccine Technology the Key to Hesitancy?". 2021-06-17. https://www.medpagetoday.com/special-reports/exclusives/93166. 
  7. ↑ King, Anthony (2021-02-04). "Covid vaccination efforts bolstered by trial results from J&J and Novavax" (in en). https://www.chemistryworld.com/news/covid-vaccination-efforts-bolstered-by-trial-results-from-jandj-and-novavax/4013169.article. 
  8. ↑ Milicic, Anita (24 March 2021). "Adjuvants: the unsung heroes of vaccines" (in en). http://theconversation.com/adjuvants-the-unsung-heroes-of-vaccines-156548. 
  9. ↑ 9.0 9.1 9.2 Stertman, L; Palm, AE; Zarnegar, B; Carow, B; Lunderius Andersson, C; Magnusson, SE; Carnrot, C; Shinde, V et al. (31 December 2023). "The Matrix-M™ adjuvant: A critical component of vaccines for the 21(st) century.". Human Vaccines & Immunotherapeutics 19 (1). doi:10.1080/21645515.2023.2189885. PMID 37113023. 
  10. ↑ "Moths and tree bark: How the Novavax vaccine works" (in en). https://www.nebraskamed.com/COVID/moths-and-tree-bark-how-the-novavax-vaccine-works. 
  11. ↑ Bonam, Srinivasa Reddy; Partidos, Charalambos D.; Halmuthur, Sampath Kumar M.; Muller, Sylviane (September 2017). "An Overview of Novel Adjuvants Designed for Improving Vaccine Efficacy". Trends in Pharmacological Sciences 38 (9): 771–793. doi:10.1016/j.tips.2017.06.002. ISSN 1873-3735. PMID 28668223. 
  12. ↑ "Malaria vaccine becomes first to achieve WHO-specified 75 percent efficacy goal" (in en). https://www.sciencedaily.com/releases/2021/04/210423085702.htm. 
  13. ↑ 13.0 13.1 Borrell, Brendan (2020-10-21). "The Tree That Could Help Stop the Pandemic" (in en). https://www.theatlantic.com/science/archive/2020/10/single-tree-species-may-hold-key-coronavirus-vaccine/616792/. 
  14. ↑ Tribble, Sarah Jane (2021-07-20). "Novavax's effort to vaccinate the world, from zero to not quite warp speed" (in en). https://qz.com/2035720/can-novavax-fulfill-its-promise-of-vaccinating-the-world. 




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