Advertisement

Structure/Function Studies on QS-21, A Unique Immunological Adjuvant from Quillaja saponaria

  • Charlotte Read Kensil
  • Sean Soltysik
  • Deborah A. Wheeler
  • Jia-Yan Wu
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 404)

Abstract

QS-21 is an acylated triterpene glycoside isolated from the bark of the South American tree Quillaja saponaria Molina’. It is a potent immunological adjuvant. It has been shown to enhance antigen-specific antibody titers to a wide variety of T-dependent and T-independent antigens, including hen egg albumin (ovalbumin)2, recombinant Borrelia burgdorferi OspA and OspB3, recombinant human cytomegalovirus envelope protein gB4, and E. coli 018 polysaccharides’. Further, QS-21-adjuvanted subunit antigen vaccines stimulate a cytotoxic T lymphocyte (CTL) response6,7,8. This response is characterized by the induction of CD8+ T cells that kill target cells expressing specific antigen. Recently, QS-21 was shown to enhance antigen-specific IgM and IgG responses in a Phase I clinical study of a melanoma immunotherapeutic vaccine9.

Keywords

Critical Micellar Concentration Adjuvant Activity Major Histocompatibility Antigen Complex Quillaja Saponin Methyloctanoic Acid 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    C.R. Kensil, U. Patel, M. Lennick, and D. Marciani, Separation and characterization of saponins with adjuvant activity from Quillaja saponaria Molina cortex, J. Immunol. 146: 431 (1991).PubMedGoogle Scholar
  2. 2.
    C.R. Kensil, M.J. Newman, R.T. Coughlin, S. Soltysik, D. Bedore, J. Recchia, J.-Y. Wu, and D.J. Marciani, The use of Stimulon adjuvant to boost vaccine response, Vaccine Res. 2: 273 (1993).Google Scholar
  3. 3.
    J. Ma, P.A. Bulger, D.V. Davis, B. Perilli-Palmer, D.A. Bedore, C.R. Kensil, E.M. Young, C.-H. Hung, J.R. Seals, C.S. Pavia, and R.T. Coughlin, Impact of the saponin adjuvant QS-21 and aluminum hydroxide on the immunogenicity of recombinant OspA and OspB of Borrelia burgdorferi,. Vaccine 12: 925 (1994).PubMedCrossRefGoogle Scholar
  4. 4.
    W. Britt, J. Fay, J. Seals, and C. Kensil, Formulation of an immunogenic human cytomegalovirus vaccine: responses in mice, J. Infect. Diseases 171: 18 (1995).CrossRefGoogle Scholar
  5. 5.
    R.T. Coughlin, A. Fattom, C. Chu, A.C. White, and S. Winston, Adjuvant activity of QS-21 for experimental E. coli 018 polysaccharide vaccines, Vaccine 13: 17 (1995).PubMedCrossRefGoogle Scholar
  6. 6.
    J.-Y. Wu, B.H. Gardner, C.I. Murphy, J.R. Seals, C.R. Kensil, J. Recchia, G.A. Beltz, G.W. Newman, and M.J. Newman, Saponin adjuvant enhancement of antigen-specific immune responses to an experimental HIV-1 vaccine, J. Immunol. 148: 1519 (1992).PubMedGoogle Scholar
  7. 7.
    M.J. Newman, J.-Y. Wu, B.H. Gardner, K.J. Munroe, D. Leombruno, J. Recchia, C.R. Kensil, and R.T. Coughlin, Saponin adjuvant induction of ovalbumin-specific CD8` cytotoxic T lymphocyte responses, J. Immunol. 148: 2357 (1992).PubMedGoogle Scholar
  8. 8.
    G.E. Hancock, D.J. Speelman, P.J. Frenchick, M.M. Mineo-Kuhn, R.B. Baggs, and D.J. Hahn, Formulation of the purified fusion protein of respiratory synctial 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 (1995).PubMedCrossRefGoogle Scholar
  9. 9.
    P.O. Livingston, S. Adluri, F. Helling, T.-J. Yao, C.R. Kensil, M.J. Newman, and D. Marciani, Phase I trial of immunological adjuvant QS-21 with a GM2 ganglioside-keyhole limpet haemocyanin conjugate vaccine in patients with malignant melanoma, Vaccine 12: 1275 (1994).PubMedCrossRefGoogle Scholar
  10. 10.
    R. Higuchi and T. Komori, Structures of compounds derived from the acyl moieties of quillajasaponin, Phytochemistry 26: 2357 (1987).CrossRefGoogle Scholar
  11. 11.
    N.E. Jacobson, W.J. Fairbrother, C.R. Kensil, A. Lim, D.A. Wheeler, and M.F. Powell, Structure of the saponin adjuvant QS-21 and its base-catalyzed isomerization product by 1H- and natural abundance “C-NMR spectroscopy, Carbohydrate Research 280: 1 (1996).CrossRefGoogle Scholar
  12. 12.
    J.L. Cleland, C.R. Kensil, A. Lim, N.E. Jacobsen, L. Basa, M. Spellman, D.A. Wheeler, J.-Y. Wu, and M.F. Powell, The isomerization and formulation stability of the vaccine adjuvant QS-21, J. Pharm. Sci. 85: 22 (1996).PubMedCrossRefGoogle Scholar
  13. 13.
    J.W. Yewdell and J.R. Bennink, The binary logic of antigen processing and presentation to T cells, Cell 62: 203 (1990).PubMedCrossRefGoogle Scholar
  14. 14.
    M.D. Miller, S. Gould-Fogerite, L. Shen, R.M. Woods, S. Koenig, R.J. Mannino, and N.L. Letvin, 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 (1992).PubMedCrossRefGoogle Scholar
  15. 15.
    K. Deres, H. Schild, K. Weismüller, G. Jung, and H. Rammensee, In vivo priming of cytotoxic T lymphocytes with synthetic lipopeptide vaccine, Nature 342: 561 (1989).Google Scholar
  16. 16.
    H. Takahashi, T. Takeshita, B. Morein, S. Putney, R.N. Germain, and J.A. Berzofsky, Induction of CD8+ cytotoxic T cells by immunization with purified HIV-1 envelope protein in ISCOMs, Nature 344: 873 (1990).PubMedCrossRefGoogle Scholar
  17. 17.
    J. Recchia, M.H.A. Lurantos, J.A. Amsden, J. Storey, and C.R. Kensil, A semisynthetic Quillaja saponin as a drug delivery agent for aminoglycoside antibiotics, Pharm. Res. 12: 1917 (1995).PubMedCrossRefGoogle Scholar
  18. 18.
    D.J. Pillion, J. Recchia, P. Wang, D.J. Marciani, and C.R. Kensil, DS-1, a modified Quillaja saponin, enhances ocular and nasal absorption of insulin, J. Pharm. Sci. 84: 1276 (1995).PubMedCrossRefGoogle Scholar
  19. 19.
    M.F.Chaplin, Monosaccharides, in: Carbohydrate Analysis, a Practical Approach, M.F. Chaplin and J.F. Kennedy, eds., IRL Press, Oxford (1986).Google Scholar
  20. 20.
    M.W. Moore, F.R. Carbone, and M.J. Bevan, Introduction of soluble protein into the class I pathway of antigen processing and presentation, Cell 54: 777 (1988).PubMedCrossRefGoogle Scholar
  21. 21.
    R. Higuchi, Y. Tokimitsu, T. Fujioka, T. Komori, T. Kawasaki, and D.G. Oakenful, Structure of desacylsaponins obtained from the bark of Quillaja saponaria, Phytochemistry 26: 229 (1987).CrossRefGoogle Scholar
  22. 22.
    C.R. Kensil, S. Soltysik, U. Patel, and D.J. Marciani, 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 (1992).Google Scholar
  23. 23.
    C.R. Kensil, J.-Y. Wu, and S. Soltysik, Structural and immunological characterization of the vaccine adjuvant QS-21, in: Vaccine Design: The Subunit and Adjuvant Approach, M.F. Powell and M.J. Newman, eds., Plenum Press, New York (1995).Google Scholar
  24. 24.
    R.H. Gisler, G. Schumann, W. Sackmann, C. Pericin, MTP-PE: profile of biological activities, in: Immunomodulation by Microbial Products and Related Synthetic Compounds, Y. Yamura, S. Kotani, L. Azuma, A. Koda, and T.Shiba, eds., Excerpta Medica, Princeton (1982).Google Scholar
  25. 25.
    R. Hunter, F. Strickland, and F. Kézdy, The adjuvant activity of nonionic block polymer surfactants. I. The role of hydrophile-lipophile balance, J. Immunol. 127: 1244 (1981).PubMedGoogle Scholar
  26. 26.
    S. Soltysik, J.-Y. Wu, J. Recchia, D.A. Wheeler, M.J. Newman, R.T. Coughlin, and C.R. Kensil, Structure/function studies of QS-21 adjuvant: assessment of triterpene aldehyde and glucuronic acid roles in adjuvant function, Vaccine 13: 1403 (1995).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

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

Personalised recommendations