QS-21

Plant extract
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) 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]

Alternative and More Efficient Sources

QS-21 has been made by total chemical synthesis, but required an inefficient 76-step processs 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]


See also

References

  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 Pengfei (March 2021). "Natural and Synthetic Saponins as Vaccine Adjuvants" Vaccines 9(3):222. PMID 33807582 PMCID: PMC8001307 DOI: 10.3390/vaccines9030222.
  7. ^ a b c Y Liu et al. Genetic engineering feat coaxes yeast to produce valuable vaccine compound, Nature, 2024, DOI: 10.1038/s41586-024-07345-9
  8. ^ Martin, L.B.B., Kikuchi, S., Rejzek, M. et al. Complete biosynthesis of the potent vaccine adjuvant QS-21. Nat Chem Biol 20, 493–502 (2024).

External links

  • Quillaja extract, other uses