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Vaccine Design pp 525-541 | Cite as

Structural and Immunological Characterization of the Vaccine Adjuvant QS-21

  • Charlotte Read Kensil
  • Jia-Yan Wu
  • Sean Soltysik
Part of the Pharmaceutical Biotechnology book series (PBIO, volume 6)

Abstract

QS-21 is a triterpene glycoside “saponin” isolated from the bark of the Quillaja saponaria Molina tree, a species native to South America. The bark of this tree, particularly the saponin fraction present in the bark, has long been known as a source of immune stimulators that can be used as vaccine adjuvants. Espinet (1951) noted the adjuvant activity of plant saponins to enhance the potency of foot-and-mouth disease vaccines. A number of commercially available complex saponin extracts were developed for adjuvant use. Not all of these extracts were effective as adjuvants. Dalsgaard (1970) showed that a correlation exists between adjuvant activity and the source of the saponin, and that the most adjuvantactive extracts were derived from the tree Quillaja saponaria. The use of Quillaja saponins as adjuvants has been reviewed by Campbell and Peerbaye (1992).

Keywords

Aluminum Hydroxide Triterpene Glycoside Adjuvant Effect Adjuvant Activity Muramyl Dipeptide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Allison, A. C., and Byars, N. E., 1986, An adjuvant formulation that selectively elicits the formation of antibodies of protective isotypes by cell-mediated immunity, J. Immunol. Methods 95:157.PubMedCrossRefGoogle Scholar
  2. Campbell, J. B., and Peerbaye, Y. A., 1992, Saponin, Res. Immunol. 143(5):526–530.PubMedCrossRefGoogle Scholar
  3. Coughlin, R. T., Chu, C., Fattom, A., White, A. C., and Winston, S., 1995, Adjuvant activity of QS-21 for experimental E. coli 018 Polysaccharide vaccines, Vaccine 13: 17–21.PubMedCrossRefGoogle Scholar
  4. Dalsgaard, K., 1970, Thin-layer Chromatographic fingerprinting of commercially available saponins, Dan. Tidsskr. Farm. 44:327–331.PubMedGoogle Scholar
  5. 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.PubMedCrossRefGoogle Scholar
  6. Deres, K., Schild, H., Wiesmuller, K., Jung, G., and Rammensee, H., 1989, In vivo priming of cytotoxic T lymphocytes with synthetic lipopeptide vaccine, Nature 342:561–564.PubMedCrossRefGoogle Scholar
  7. Espinet, R. G., 1951, Nouveau vaccin antiaphteux a complexe glucoviral, Gac. Vet. 13:268.Google Scholar
  8. Freund, J., 1956, The mode of action of immunological adjuvants, Adv. Tuberc. Res. 7:130–148.Google Scholar
  9. Higuchi, R., Tokimitsu, Y., and Komori, T., 1988, An acylated triterpenoid saponin from Quillaja saponaria, Phytochemistry 27:1165–1168.CrossRefGoogle Scholar
  10. Kensil, C. R., and Marciani, D. J., 1991, Saponin adjuvant, U.S. Patent #5,057,540.Google Scholar
  11. Kensil, C. R., Patel, U., Lennick, M., and Marciani, D., 1991a, Separation and characterization of saponins with adjuvant activity from Quillaja saponaria Molina cortex, J. Immunol. 146:431–437.PubMedGoogle Scholar
  12. Kensil, C. R., Barrett, C., Kushner, N., Beltz, G., Storey, J., Patel, U., Recchia, J., Aubert, A., and Marciani, D., 1991b, Development of a genetically engineered vaccine against feline leukemia virus infection, J. Am. Vet. Med. Assoc. 199:1423–1427.PubMedGoogle Scholar
  13. Kensil, C. R., Soltysik, S., Patel, U., and Marciani, D. J., 1992, Structure/function relationship in adjuvants from Quillaja saponaria Molina, in: Vaccines 92 (F. Brown, R. M. Chanock, H. S. Ginsberg, and R. A. Lerner, eds.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 35–40.Google Scholar
  14. Kensil, C. R., Newman, M. J., Coughlin, R. T., Soltysik, S., Bedore, D., Recchia, J., Wu, J.-Y., and Marciani, D. J., 1993, The use of Stimulon adjuvant to boost vaccine response, Vaccine Res. 2:273–281.Google Scholar
  15. Kensil, C. R., Bedore, A., Cleland, J. L., Lim, A., Jacobsen, N., and Powell, M. F., 1995, Stability of QS-21 in aqueous solutions, (in preparation).Google Scholar
  16. Kersten, G. F. A., Teerlink, T., Derks, H. J. G. M., Verkleij, A. J., van Wezel, T. L., Crommelin, D. J. A., and Beuvery, E. C., 1988, Incorporation of the major outer membrane protein of Neisseria gonorrhoeae in saponin-lipid complexes (Iscoms): Chemical analysis, some structural features, and comparison of their immunogenicity with three other antigen delivery systems, Infect. Immun. 56:432–438.PubMedGoogle Scholar
  17. Kirkley, J. E., Naylor, P. H., Marciani, D. J., Kensil, C. R., Newman, M. J., and Goldstein, A. L., 1992, QS-21 augments the antibody response to a synthetic peptide vaccine compared to alum, in: Combination Therapies (A. L. Goldstein and E. Garaci, eds.), Plenum Press, New York, pp. 231–236.CrossRefGoogle Scholar
  18. Klaus, G. G. B., Pepys, M. B., Kitajima, K., and Askonas, B. A., 1979, Activation of mouse complement by different classes of mouse antibody, Immunology 38:687–695.PubMedGoogle Scholar
  19. Livingston, P. O., 1993, Approaches to augmenting the IgG antibody response to melanoma ganglioside vaccines, Ann. N.Y. Acad. Sci. 690:204–213.PubMedCrossRefGoogle Scholar
  20. Livingston, P. O., Koganty, R., Longenecker, B. M., Lloyd, K. O., and Calves, M., 1992, Studies on the immunogenicity of synthetic and natural Thomsen-Friedenreich (TF) antigens in mice: Augmentation of the response by Quil A and Saf-M adjuvants and analysis of the specificity of the responses, Vaccine Res. 1(2):99–109.Google Scholar
  21. Livingston, P. O., Adluri, S., Helling, F., Yao, T.-J., Kensil, C. R., Newman, M. J., and Marciani, D., 1994, Phase I trial of immunological adjuvant QS-21 with a GM2 ganglioside-KLH conjugate vaccine in patients with malignant melanoma, Vaccine 12:1275–1280.PubMedCrossRefGoogle Scholar
  22. Ma, J., Bulger, P. A., Davis, D.vR., Perilli-Palmer, B., Bedore, D. A., Kensil, C. R., Young, E. M., Hung, C. H., Seals, J. R., Pavia, C. S., and Coughlin, R. T., 1994, Impact of the saponin adjuvant QS-21 and aluminum hydroxide on the immunogenicity of recombinant OspA and OspB of Borrelia burgdorferi, Vaccine 12:925–932.PubMedCrossRefGoogle Scholar
  23. Maraskovsky, E., Chen, W.-F., and Shortman, K., 1989, IL-2 and IFN-γ are two necessary lymphokines in the development of cytolytic T cells, J. Immunol. 143:1210–1214.PubMedGoogle Scholar
  24. Marciani, D. J., Kensil, C. R., Beltz, G. A., Hung, C.-H., Cronier, J., and Aubert, A., 1991, Genetically-engineered subunit vaccine against feline leukemia virus: protective immune response in cats, Vaccine 9:89–96.PubMedCrossRefGoogle Scholar
  25. Miller, M. D., Gould-Fogerite, S., Shen, L., Woods, R. M., Koenig, S., Mannino, R. J., and Letvin, N. L., 1992, Vaccination of rhesus monkeys with synthetic peptide in a fusogenic proteoliposome elicits simian immunodeficiency virus-specific CD8+ cytotoxic T lymphocytes, J. Exp. Med. 176:1739–1744.PubMedCrossRefGoogle Scholar
  26. Mitchell, M. D., Kan-Mitchell, J., Kempf, R. A., Harel, W., Shan, H., and Lind, S., 1988, Active specific immunotherapy for melanoma: Phase I trial of allogeneic lysates and a novel adjuvant, Cancer Res. 48:5883–5889.PubMedGoogle Scholar
  27. Morein, B., Sundquist, B., Hoglund, S., Dalsgaard, K., and Osterhaus, A., 1984, Iscom, a novel structure for antigenic presentation of membrane proteins from enveloped viruses, Nature 308:457–460.PubMedCrossRefGoogle Scholar
  28. Newman, M. J., Wu, J.-Y, Gardner, B. H., Munroe, K. J., Leombruno, D., Recchia, J., Kensil, C. R., and Coughlin, R. T., 1992a, Saponin adjuvant induction of ovalbumin-specific CD8+ cytotoxic T lymphocyte responses, J. Immunol. 148:2357–2362.PubMedGoogle Scholar
  29. Newman, M. J., Wu, J.-Y., Coughlin, R. T., Murphy, C. I., Seals, J. R., Wyand, M. S., and Kensil, C. R., 1992b, Immunogenicity and toxicity testing of an experimental HIV-1 vaccine in nonhuman primates, AIDS Res. Hum. Retroviruses 8:1413–1418.PubMedGoogle Scholar
  30. Newman, M. J., Munroe, K. J., Anderson, C. A., Murphy, C. I., Panicali, D. L., Seals, J. R., Wu, J.-Y., Wyand, M. S., and Kensil, C. R., 1994, Induction of antigen-specific cytotoxic T lymphocytes using subunit SIV mac251 gag and env vaccines containing QS-21 saponin adjuvant, AIDS Res. Hum. Retroviruses 10(7):853–861.PubMedGoogle Scholar
  31. Powell, M. F., Cleland, J. L., Murthy, K., Eastman, D. J., Lim, A., Newman, M. J., Nunberg, J. H., Weissburg, R. P., Vennari, J. C., Wrin, T., and Berman, P. W., 1994, Immunogenicity and HIV-1 virus neutralization of the MN rgpl20/HIV-l QS-21 vaccine in baboons, AIDS Res. Hum. Retroviruses 10(Suppl. 1):S85–S88.Google Scholar
  32. Shirai, M., Pendleton, C. D., Ahlers, J., Takeshita, T., Newman, M., and Berzofsky, J. A., 1994, Helper-cytotoxic T lymphocyte (CTL) determinant linkage required for priming of anti-HIV CD8+ CTL in vivo with peptide vaccine constructs, J. Immunol. 152:549–556.PubMedGoogle Scholar
  33. Snapper, C. M., and Paul, W. E., 1987, Interferon-γ and B cell stimulatory factor-1 reciprocally regulate Ig isotype production, Science 236:944–947.PubMedCrossRefGoogle Scholar
  34. Stevens, T. L., Bossie, A., Sanders, V. M., Fernandez-Botran, R., Coffman, R. L., Mossman, T. R., and Vitetta, E. S., 1988, Regulation of antibody isotype secretion by subsets of antigen-specific helper T cells, Nature 334:255–258.PubMedCrossRefGoogle Scholar
  35. Strobbe, R., Charlier, G., van Aert, A., Debecq, J., and Leunen, J., 1974, Studies about the adjuvant activity of saponin fractions in foot-and-mouth disease vaccine. II. Irritant and adjuvant activity of saponin fractions obtained by chromatography on Sephadex G100, Arch. Exp. Vet. Med. 28:385–392.Google Scholar
  36. Takahashi, H., Takeshita, T., Morein, B., Putney, S., Germain, R. N., and Berzofsky, J. A., 1990, Induction of CDS+ cytotoxic T cells by immunization with purified HIV-1 envelope protein in ISCOMs, Nature 344:873–875.PubMedCrossRefGoogle Scholar
  37. Van Nest, G. A., Steimer, K. S., Haigwood, N. L., Burke, R. L., and Ott, G., 1992, Advanced adjuvant formulations for use with recombinant subunit vaccines, in: Vaccines 92: Modern Approaches to New Vaccines (R. M. Chanock, R. A. Lerner, R Brown, and H. Ginsburg, eds.), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 57–62.Google Scholar
  38. White, A. C., Cloutier, P., and Coughlin, R. T., 1991, A purified saponin acts as an adjuvant for a T-independent antigen, in: Immunobiology of Proteins and Peptides, Vol. VI (M. Z. Atassi, ed.), Plenum Press, New York, pp. 207–210.CrossRefGoogle Scholar
  39. Wu, J.-Y., Gardner, B. H., Murphy, C. I., Seals, J. R., Kensil, C. R., Recchia, J., Beltz, G. A., Newman, G. W., and Newman, M. J., 1992, Saponin adjuvant enhancement of antigen-specific immune responses to an experimental HIV-1 vaccine, J. Immunol. 148:1519–1525.PubMedGoogle Scholar
  40. Wu, J.-Y., Gardner, B. H., Kushner, N. N., Pozzi, L. M., Kensil, C. R., Cloutier, P. A., Coughlin, R. T., and Newman, M. J., 1994, Accessory cell requirements for saponin adjuvant-induced class I MHC antigen-restricted cytotoxic T-lymphocytes, Cell. Immunol. 154:393–406.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Charlotte Read Kensil
    • 1
  • Jia-Yan Wu
    • 1
  • Sean Soltysik
    • 1
  1. 1.Cambridge Biotech CorporationWorcesterUSA

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