QS-21



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) 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.

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. This semi-synthetic approach has also facilitated experimentation with alternative acyl chain compositions.

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 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.

Alternative sources
QS-21 has been made by total chemical synthesis, but required an inefficient 76-step processs that is not commercially viable. 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. More recently 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.’