Abstract
QS-21 is an immunological adjuvant derived from a natural source: the bark of the South American tree Quillaja saponaria Molina. Crude extracts of Quillaja saponaria bark were found to have adjuvant activity in foot-andmouth disease vaccines in cattle (1). These extracts consisted of a complex mixture of tannins, polyphenolics, and triterpene glycoside “saponins.” The adjuvant activity was determined to be in the saponin fraction (2). This was later fractionated by high-performance liquid chromatography (HPLC) into at least 23 different triterpene glycoside saponins with a varying range of biological activity for adjuvanticity, surfactant properties, and toxicity (3). QS-21 was identified as a saponin with potent adjuvant activity and low toxicity (3). It can be purified to near homogenity via preparative HPLC. The high level of purity and standardization of the QS-21 saponin adjuvant has enabled evaluation of this compound in clinical trials of experimental vaccines.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Espinet, R. G. (1951) Nouveau vaccin antiaphteux a complexe glucoviral. Gac. Vet. 13, 268.
Dalsgaard, K. (1974) Saponin adjuvants. III. Isolation of a substance from Quillaja saponaria Molina with adjuvant activity in foot-and-mouth disease vaccines. Arch. Gesamte Virusforsch. 44, 243–254.
Kensil, C. R., Patel, U., Lennick, M., and Marciani, D. (1991) Separation and characterization of saponins with adjuvant activity from Quillaja saponariaMolina cortex. J. Immunol. 146, 431–437.
Ma, J., Bulger, P. A., Davis, D. R., Perilli-Palmer, B., Bedore, D. A., Kensil, C. R., et al. (1994) Impact of the saponin adjuvant QS-21 and aluminium hydroxide on the immunogenicity of recombinant OspA and OspB of Borrelia burgdorferi. Vaccine 12, 925–932.
Hancock, G. E., Speelman, D. J., Frenchick, P. J., Mineo-Kuhn, M. M., Baggs, R. B., and Hahn, D. J. (1995) Formulation of the purified fusion protein of respiratory syncytial virus with the saponin QS-21 induces protective immune responses in Balb/c mice that are similar to those generated by experimental infection. Vaccine 13, 391–400.
Cleland, J. L., Barron, L., Daugherty, A., Eastman, D., Kensil, C., Lim, A., et al. (1996) Development of a single-shot subunit vaccine for HIV-1. 3. Effect of adjuvant and immunization schedule on the duration of the humoral immune response to recombinant MN gp120. J. Pharm. Sci. 85, 1350–1357.
Newman, M. J., Wu, J. Y., Coughlin, R. T., Murphy, C. I., Seals, J. R., Wyand, M. S., et al. (1992) Immunogenicity and toxicity testing of an experimental HIV-1 vaccine in nonhuman primates. AIDS Res. Hum. Retroviruses 8, 1413–1418.
Powell, M. F., Cleland, J. L., Eastman, D. J., Lim, A., Murthy, K., Newman, M. J., et al. (1994) Immunogenicity and HIV-1 virus neutralization of MN recombinant glycoprotein 120/HIV-1 QS21 vaccine in baboons. AIDS Res. Hum. Retroviruses 10(Suppl.2), S105–S108.
Coughlin, R. T., Fattom, A., Chu, C., White, A. C., and Winston, S. (1995) Adjuvant activity of QS-21 for experimental E. coli 018 polysaccharide vaccines. Vaccine 13, 17–21.
Sasaki, S., Sumino, K., Hamajima, K., Fukushima, J., Ishii, N., Kawamoto, S., et al. (1998) Induction of systemic and mucosal immune responses to human immunodeficiency virus type 1 by a DNA vaccine formulated with QS-21 saponin adjuvant via intramuscular and intranasal routes. J. Virol. 72, 4931–939.
Newman, M. J., Wu, J. Y., Gardner, B. H., Munroe, K. J., Leombruno, D., Recchia, J., et al. (1992) Saponin adjuvant induction of ovalbumin-specific CD8+ cytotoxic T lymphocyte responses. J. Immunol. 148, 2357–2362.
Kensil, C. R., Wu, J. Y., and Soltysik, S. (1995) Structural and immunological characterization of the vaccine adjuvant QS-21. Pharm. Biotechnol. 6, 525–541.
Helling, F., Zhang, S., Shang, A., Adluri, S., Calves, M., Koganty, R., et al. (1995) GM2-KLH conjugate vaccine: increased immunogenicity in melanoma patients after administration with immunological adjuvant QS-21. Cancer Res. 55, 2783–2788.
Livingston, P. O., Adluri, S., Helling, F., Yao, T. J., Kensil, C. R., Newman, M. J., et al. (1994) Phase 1 trial of immunological adjuvant QS-21 with a GM2 gangliosidekeyhole limpet haemocyanin conjugate vaccine in patients with malignant melanoma. Vaccine 12, 1275–1280.
Stoute, J. A., Slaoui, M., Heppner, D. G., Momin, P., Kester, K. E., Desmons, P., et al. (1997) A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodiumfalciparum malaria. The N. Eng. J. Med. 9, 86–91.
Jacobsen, N. E., Fairbrother, W. J., Kensil, C. R., Lim, A., Wheeler, D. A., and Powell, M. F. (1996) Structure of the saponin adjuvant QS-21 and its basecatalyzed isomerization product by 1H and natural abundance 13C NMR spectroscopy. Carbohydr. Res. 280, 1–14.
Kensil, C. R., Newman, M. J., Coughlin, R. T., Soltysik, S., Bedore, D., Recchia, J., et al. (1993) The use of Stimulon adjuvant to boost vaccine response. Vaccine Res. 2, 273–281.
Cleland, J. L., Kensil, C. R., Lim, A., Jacobsen, N. E., Basa, L., Spellman, M., et al. (1996) Isomerization and formulation stability of the vaccine adjuvant QS-21. J. Pharm. Sci. 85, 22–28.
Kensil, C. R., Soltysik, S., Wheeler, D. A., and Wu, J. Y. (1996)Structure/function studies on QS-21, a unique immunological adjuvant from Quillaja saponaria.Adv. Exp. Med. Biol. 404, 165–172.
Powell, M. F., Eastman, D. J., Lim, A., Lucas, C., Peterson, M., Vennari, J., et al. (1995) Effect of adjuvants on immunogenicity of MN recombinant glycoprotein 120 in guinea pigs. AIDS Res. Hum. Retroviruses 11, 203–209.
Cleland, J. L., Powell, M. F., Lim, A., Barron, L., Berman, P. W., Eastman, D. J., et al. (1994) Development of a single-shot subunit vaccine for HIV-1. AIDS Res. Hum. Retroviruses 10(Suppl. 2), S21–S26.
Cleland, J. L., Lim, A., Barron, L., Duenas, E. T., and Powell, M. F. (1997) Development of a single-shot subunit vaccine for HIV-1: Part 4. Optimizing microencapsulation and pulsatile release of MN rgp120 from biodegradable microspheres. J. Controlled Release 47, 135–150.
Murphy, C. I., McIntire, J. R., V.R.Davis, D., Hodgon, H., Seals, J. R., and Young, E. (1993) Enhanced expression, secretion, and large-scale purification of recombinant HIV-1 gp120 in insect cells using the baculovirus egt and p67 signal peptides. Protein Express. Purif. 4, 349.
Takahashi, H., Cohen, J., Hosmalin, A., Cease, K. B., Houghten, R., Cornette, J.,et al. (1988) An immunodominant epitope of the HIV gp160 envelope glycoprotein recognized by class I MHC molecule-restricted cytotoxic T lymphocytes.Proc. Natl. Acad. Sci. USA 85, 3105.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2000 Humana Press Inc.
About this protocol
Cite this protocol
Read Kensil, C. (2000). QS-21 Adjuvant. In: O’Hagan, D.T. (eds) Vaccine Adjuvants. Methods in Molecular Medicine™, vol 42. Springer, Totowa, NJ. https://doi.org/10.1385/1-59259-083-7:259
Download citation
DOI: https://doi.org/10.1385/1-59259-083-7:259
Publisher Name: Springer, Totowa, NJ
Print ISBN: 978-0-89603-735-9
Online ISBN: 978-1-59259-083-4
eBook Packages: Springer Protocols