thumb|right|400px|Basic structure of QS-21, consisting of a quillaic acid triterpene (black) substituted with a branched trisaccharide (blue) and a linear tetrasaccharide (green), which is in turn connected to an acyl chain (red) via a hydrolytically labile ester. QS-21 is a 65:35 mixture of the [[w:Apiose|Apiose- and the 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.

  • AS-01 (also known as AS01<sub>E</sub>), 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.
  • 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.

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.

References

  • Quillaja extract, other uses