QS-21
QS-21 is a purified plant extract used as a vaccine adjuvant. It is derived from the soap bark tree, which is native to the countries of Chile, Peru, and Bolivia. The crude drug 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, 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 sealed inside cholestrol-based liposomes.
- Army Liposome Formulation Q, MPL and QS-21 sealed inside cholesterol-based liposomes produced by the US Army. Designed to be unencumbered by AS-01 patents, it was created in 2019 by enhancing the existing, MPL-based Army Liposome Formulation with QS-21.
- 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 of 1984 and ISCOMATRIX, two forerunners to Matrix-M
Tree bark
A semi-synthesis strategy from 2013 relies on purifying the prosapogenin part of the molecule and adding the rest of QS-21 synthetically, doubling the yield over simple isolation. 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 version of QS-21 to the US FDA in 2023. An animal study using this cpc-QS-21 was published in 2024.