QS-21

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 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.[1] The crude drug (Quillajae cortex, Quillaia) 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. As of 2002, 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]

  1. ^ a b c Ragupathi G, Gardner JR, Livingston PO, Gin DY (2013). "Natural and synthetic saponin adjuvant QS-21 for vaccines against cancer". Expert Rev Vaccines. 10 (4): 463–70. doi:10.1586/erv.11.18. PMC 3658151. PMID 21506644.
  2. ^ Max Wichtl, ed. (2004). Herbal Drugs and Phytopharmaceuticals: A Handbook for Practice on a Scientific Basis. Medpharm Publishers. p. 492. ISBN 3-88763-100-5.
  3. ^ Chea EK, Fernández-Tejada A, Damani P, Adams MM, Gardner JR, Livingston PO, Ragupathi G, Gin DY (2013). "Synthesis and preclinical evaluation of QS-21 variants leading to simplified vaccine adjuvants and mechanistic probes". J Am Chem Soc. 134 (32): 13448–57. doi:10.1021/ja305121q. PMC 3436428. PMID 22866694.
  4. ^ "SHINGRIX package insert" (PDF). Food and Drug Administration. Retrieved 7 April 2019.
  5. ^ Viswanath, P. (April 29, 2021). "COVID-19: Raw material crunch pushes vaccine makers to look at indigenization". moneycontrol.com. Retrieved 30 April 2021.
  6. ^ Wang P (March 2021). "Natural and Synthetic Saponins as Vaccine Adjuvants". Vaccines. 9 (3). doi:10.3390/vaccines9030222. PMC 8001307. PMID 33807582.