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.[1] The crude drug (Quillajae cortex) is imported from Peru and Chile.[2]
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.[1]
Isolation of QS-21 destroys the soap bark tree, prompting governments to regulate industrial extraction. A semi-synthesis strategy relies on purifying the prosapogenin (triterpene and branched trisaccharide) part of the molecule and adding the rest of QS-21 synthetically, doubling the yield.[1] This semi-synthetic approach has also facilitated experimentation with alternative acyl chain compositions.[3]
QS-21 has been clinically evaluated as a vaccine adjuvant., it had been tested in more than 3000 patients in 60 clinical trials. It is a component of the AS-01 adjuvant used in the Shingrix vaccine[4] and of the Matrix-M adjuvant used in the Novavax COVID-19 vaccine.
Agenus is the sole US-manufacturer of an FDA-approved, patented extract. Supplies are tightly controlled, and the United States has invoked the 1950 Defense Production Act to preserve vaccine raw materials for its own companies.[5] [6]
QS-21 has been made by total chemical synthesis, but required an inefficient 76-step process that is not commercially viable.[7] Several companies have succeeded in isolating the compound from plant tissue cultures of the soapbark plant. 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.[8] More recently an international team of collaborators succeed in engineering yeast to perform the complete biosynthesis of QS-21.[7] 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.’[7]