QS-21

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Plant extract

title: "QS-21" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["adjuvants", "saponins", "triterpene-glycosides"] description: "Plant extract" topic_path: "general/adjuvants" source: "https://en.wikipedia.org/wiki/QS-21" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Plant extract ::

::figure[src="https://upload.wikimedia.org/wikipedia/commons/4/4c/QS-21.svg" caption="Xylose]]-substituted variants of above molecule."] ::

QS-21 is a purified plant extract used as a vaccine adjuvant. It is derived from the soap bark tree (Quillaja saponaria), which is native to the countries of Chile, Peru, and Bolivia. The crude drug (Quillajae cortex, Quillaia) is imported from Peru and Chile.

The extract contains water-soluble triterpene glycosides, which are members of a family of plant-based compounds called saponins. It has been tested as an adjuvant in various vaccines in attempts to improve their efficacy. It is believed to enhance both humoral and cell-mediated immunity.

Use

QS-21 has been clinically evaluated as a vaccine adjuvant. , it had been tested in more than 3000 patients in 60 clinical trials.

Direct, unencapsulated QS-21 is very liable to hydrolyse. It also causes immediate pain at injection site and, in vitro, causes hemolysis. All of these can be prevented by packaging QS-21 into lipid-based particles, which also have the added advantage of targeting its delivery to phagocytes. It is part of:

  • AS-01 (also known as AS01E), GSK's adjuvant used in the Shingrix vaccine, the RTS,S vaccine, and the M72/AS01E vaccine. AS-01 consists of QS-21 and 3-O-desacyl-4'-monophosphoryl lipid A (MPL) sealed inside cholestrol-based liposomes.
  • Army Liposome Formulation Q (ALFQ), MPL and QS-21 sealed inside cholesterol-based liposomes produced by the US Army.
  • Matrix-M, Novavax's adjuvant used in the Novavax COVID-19 vaccine. Matrix-M contains a mixture of soapbark saponins sealed in nanoparticles made of cholesterol and phospholipid; one of these saponins is QS-21.
  • Immune-stimulating complex (ISCOM) of 1984 and ISCOMATRIX (CSL Limited, 2012), two forerunners to Matrix-M

Sources

Tree bark

Isolation of QS-21 destroys the soap bark tree, prompting governments to regulate industrial extraction.

A semi-synthesis strategy from 2013 relies on purifying the prosapogenin (triterpene and branched trisaccharide) part of the molecule and adding the rest of QS-21 synthetically, doubling the yield over simple isolation (amount produced from a given amount of tree bark). This semi-synthetic approach has also facilitated experimentation with alternative acyl chain compositions.

In 2017, FDA approved the Shingrix vaccine which makes use of the extracted form of QS-21 made by Agenus under the trade name Stimulon. Agenus remains the sole US manufacturer of FDA-approved QS-21 as of 2021.

Sustainable biomass pruning

Saponins, including QS-21, are present throughout the biomass of Quillaja saponaria Mol., though typically at lower concentrations in the branches, trunk, and leaves compared to the bark. However, these non-bark components represent a significantly larger biomass volume and thus contribute a higher total yield of saponins. The practice of pruning Quillaja trees to harvest this biomass for saponin extraction has been used sustainably by the food industry since 2000. In 2022, the company Q-Vant communicated having achieved the fractioning of QS-21 from any part of the Quillaja plant, including branches and trunks obtained through renewable pruning methods.

Plant tissue culture

Several companies have succeeded in isolating the compound from plant tissue cultures of the soapbark plant.

The aforementioned Agenus created a spin-off company called SaponiQx to manage its QS-21 business. SaponiQx submitted the Master File for its cultured plant cell (cpc) version of QS-21 to the US FDA in 2023. An animal study using this cpc-QS-21 was published in 2024.

Transgenic tobacco

In 2024, a team at the John Innes Centre in Norwich, UK identified the complete 20-step biosynthetic pathway of QS-21 and cloned it into tobacco.

Transgenic yeast

In 2024, an international team of collaborators succeed in engineering yeast to perform the complete biosynthesis of QS-21. One of the scientists pointed out that the yeast process is around 1000 times faster than trees because only mature trees produce QS-21. "Even at the levels we're producing it, it's cheaper than producing it from the plant."

Total synthesis

QS-21 has been made by total chemical synthesis, but required an inefficient 76-step process that is not commercially viable. This is not unlike the total chemical synthesis of many other complex biomolecules, which served mainly to confirm their structure rather than to produce an economically-viable source.

References

References

  1. (2013). "Natural and synthetic saponin adjuvant QS-21 for vaccines against cancer". Expert Rev Vaccines.
  2. (2004). "Herbal Drugs and Phytopharmaceuticals: A Handbook for Practice on a Scientific Basis". Medpharm Publishers.
  3. (31 December 2023). "The Matrix-M™ adjuvant: A critical component of vaccines for the 21(st) century.". Human Vaccines & Immunotherapeutics.
  4. "SHINGRIX package insert". [[Food and Drug Administration]].
  5. (3 March 2020). "Army Liposome Formulation (ALF) family of vaccine adjuvants". Expert Review of Vaccines.
  6. (8 October 2019). "US10434167B2 Non-toxic adjuvant formulation comprising a monophosphoryl lipid A (MPLA)-containing liposome composition and a saponin".
  7. (March 2021). "Natural and Synthetic Saponins as Vaccine Adjuvants". Vaccines.
  8. (2013). "Synthesis and preclinical evaluation of QS-21 variants leading to simplified vaccine adjuvants and mechanistic probes". J Am Chem Soc.
  9. "FDA Approves GSK's Shingles Vaccine with Agenus' QS-21 Stimulon® Adjuvant".
  10. "First QS-21 Royalty Payment Due to Agenus is Triggered".
  11. (2000). "Monografía de Quillay, Quillaja saponaria". INFOR : FIA : INDAP.
  12. (July 1999). "Industrial uses and sustainable supply ofQuillaja saponaria (Rosaceae) saponins". Economic Botany.
  13. Marino, Dan. (2022-01-12). "Q-VANT Biosciences Launches to Solve the Pharmaceutical Industry Problem of Limited Quillaja Saponin-Based Adjuvants for Life-Saving Vaccines".
  14. "SaponiQx Announces Breakthrough in Scaling Up of STIMULON™ Cultured Plant Cell Adjuvant".
  15. (20 December 2024). "Plant Cell Culture-Derived Saponin Adjuvant Enhances Immune Response Against a Stabilized Human Metapneumovirus Pre-Fusion Vaccine Candidate". Vaccines.
  16. (April 2024). "Complete biosynthesis of the potent vaccine adjuvant QS-21". Nat Chem Biol.
  17. (May 2024). "Complete biosynthesis of QS-21 in engineered yeast". Nature.

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adjuvantssaponinstriterpene-glycosides