QS-21

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QS-21, Api: β-D- apiofuranosyl ; Xyl: α- L - rhamnopyranosyl

QS-21 is an extract from the soap bark tree Quillaja saponaria , which is used as an adjuvant in vaccines . It is one of the most powerful adjuvants.

properties

QS-21 contains saponins . The saponins contained consist of a the central fucose residue acylated linear tetrasaccharide , which on the C28-atom of a triterpene ( quillaic is bound). Quillajic acid also has a branched trisaccharide on the C3 atom . The three inner saccharides of the tetrasaccharide are necessary for the adjuvant effect of the saponins. The saponins mainly contained in the extract are QS-21- apiose and QS-21- xylose in a ratio of 2: 1 and differ in the terminal saccharide. QS-21 tends to hydrolyze the acyl group , which reduces the adjuvant effect. A synthetic variant of QS-21 has been described, but did not show the same adjuvant effect. Together with 3- O -desacyl-4'-monophosphoryl lipid A ( MPL ), QS-21 is part of the adjuvant AS01 ( liposomal ) and AS02 ( emulsion ).

QS-21 enhances both the humoral immune response and the cellular immune response . The NLRP3 inflammasome is also activated in mice, which enables the release of capsase-1 -dependent cytokines .

Extraction

QS-21 is purified from the aqueous QuilA extract of the bark of Q. saponaria Molina by RP- HPLC . Among the factions of QuilA , QS-7, QS-17, Q-18 and QS-21 are adjuvant. Since the adjuvant fraction QS-18, which occurs in the largest amount, is toxic in mice , the less toxic adjuvant fractions QS-7 and QS-21 can be used. QS-21 is the larger of the two fractions.

More than 50 QS-21 analogs were synthesized.

use

QS-21 is part of the herpes zoster dead vaccine Shingrix . It is also being investigated as an adjuvant in cancer vaccines and malaria vaccines such as RTS, S.

history

The adjuvant effect of the Quillaja extract QuilA was first described by Gaston Ramon in 1925 , in addition to the adjuvant effect of breadcrumbs, tapioca flour and soy starch in the diphtheria vaccination of horses . From 1964, the saponins from QuilA were examined in more detail. Due to toxicity , hemolysis, and chemical instability, QS-21 was not approved for human use until the early 2000s. The herpes zoster vaccine Shingrix , which contains QS-21, was approved in the US in 2017 and in the EU in 2018.

literature

  • SR Bonam, CD Partidos, SK Halmuthur, S. Muller: An Overview of Novel Adjuvants Designed for Improving Vaccine Efficacy. In: Trends in pharmacological sciences. Volume 38, Number 9, September 2017, pp. 771-793, doi : 10.1016 / j.tips.2017.06.002 , PMID 28668223 .
  • DJ Marciani: Is fucose the answer to the immunomodulatory paradox of Quillaja saponins? In: International immunopharmacology. Volume 29, number 2, December 2015, pp. 908-913, doi : 10.1016 / j.intimp.2015.10.028 , PMID 26603552 .

Individual evidence

  1. ↑ a b c d e f E. K. Chea, A. Fernández-Tejada, P. Damani, MM Adams, JR Gardner, PO Livingston, G. Ragupathi, DY Gin: Synthesis and preclinical evaluation of QS-21 variants leading to simplified vaccine adjuvants and mechanistic probes. In: Journal of the American Chemical Society. Volume 134, number 32, August 2012, pp. 13448-13457, doi : 10.1021 / ja305121q , PMID 22866694 , PMC 3436428 (free full text).
  2. ↑ a b c d e G. Ragupathi, JR Gardner, PO Livingston, DY Gin: Natural and synthetic saponin adjuvant QS-21 for vaccines against cancer. In: Expert review of vaccines. Volume 10, number 4, April 2011, pp. 463-470, doi : 10.1586 / erv.11.18 , PMID 21506644 , PMC 3658151 (free full text).
  3. ^ A b c Marie-Aleth Lacaille-Dubois: Updated insights into the mechanism of action and clinical profile of the immunoadjuvant QS-21: A review . In: Phytomedicine (=  90th birthday of Professor Hildebert Wagner ). tape 60 , July 1, 2019, p. 152905 , doi : 10.1016 / j.phymed.2019.152905 .
  4. ↑ a b A. M. Didier Laurent, B. Laupèze, A. Di Pasquale, N. Hergli, C. Collignon, N. Garçon: adjuvant system AS01: helping to overcome the challenges of modern vaccines. In: Expert review of vaccines. Volume 16, number 1, January 2017, pp. 55-63, doi : 10.1080 / 14760584.2016.1213632 , PMID 27448771 .
  5. ^ N. Garçon, M. Van Mechelen: Recent clinical experience with vaccines using MPL- and QS-21-containing adjuvant systems. In: Expert review of vaccines. Volume 10, Number 4, April 2011, pp. 471-486, doi : 10.1586 / erv.11.29 , PMID 21506645 .
  6. ↑ a b C. R. Kensil, U. Patel, M. Lennick, D. Marciani: Separation and characterization of saponins with adjuvant activity from Quillaja saponaria Molina cortex. In: Journal of Immunology. Volume 146, Number 2, January 1991, pp. 431-437, PMID 1987271 .
  7. ^ Marie-Aleth Lacaille-Dubois: Updated insights into the mechanism of action and clinical profile of the immunoadjuvant QS-21: A review . In: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology . tape 60 , July 2019, p. 152905 , doi : 10.1016 / j.phymed.2019.152905 , PMID 31182297 .
  8. ↑ G. Ramon: Sur l'augmentation anormale de L'antitoxine chez les chevaux producteurs de serum antidiphtherique. In: Bull. Soc. Centr. Med. Vet. (1925), Vol. 101, pp. 227-234.
  9. ↑ HJ Warshakoon, JD Hood, MR Kimbrell, S. Malladi, WY Wu, NM Shukla, G. Agnihotri, D. Sil, SA David: Potential adjuvantic properties of innate immune stimuli. In: Human vaccines. Volume 5, Number 6, June 2009, pp. 381-394, PMID 19270494 .
  10. ↑ R. Richou, R. Jensen, C. Belin: [RESEARCH ON SAPONIN, AN ADJUVANT SUBSTANCE WHICH Stimulates IMMUNITY. I]. (in french) In: Revue d'immunologie et de thérapie antimicrobienne. Volume 28, 1964 Jan-Mar, pp. 49-62, PMID 14187805 .
  11. ↑ ZI Rajput, SH Hu, CW Xiao, AG Arijo: Adjuvant effects of saponins on animal immune responses. In: Journal of Zhejiang University. Science. B. Volume 8, Number 3, March 2007, pp. 153-161, doi : 10.1631 / jzus.2007.B0153 , PMID 17323426 , PMC 1810383 (free full text).