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.[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, which has resulted in regulation of the tree by the governments where it is grown. 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; this is reported to increase the yield by 2 orders of magnitude.[1] This semi-synthetic approach has also facilitated experimentation with alternative acyl chain compositions.[3]
QS-21 has undergone clinical evaluation as an additive for various trial vaccines, including those for HIV, malaria and cancer. As of 2002[update], 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 Inc. is the sole US-manufacturer of an FDA-approved, patented extract. Supplies are tightly controlled, and the US has invoked the US Defense Production Act to preserve vaccine raw materials for its own companies.[5][6]
See also
References
- ^ 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.
- ^ 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.
- ^ 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.
- ^ "SHINGRIX package insert" (PDF). Food and Drug Administration. Retrieved 7 April 2019.
- ^ VISWANATH, P. (April 29, 2021) "COVID-19: Raw material crunch pushes vaccine makers to look at indigenization". moneycontrol.com. Retrieved 30 April 2021.
- ^ Wang Pengfei (March 2021). "Natural and Synthetic Saponins as Vaccine Adjuvants" Vaccines 9(3):222. PMID 33807582 PMCID: PMC8001307 DOI: 10.3390/vaccines9030222.