Design and synthesis of potent Quillaja saponin vaccine adjuvants.

Abstract

The success of antitumor and antiviral vaccines often requires the use of an adjuvant, a substance that significantly enhances the immune response to a coadministered antigen. Only a handful of adjuvants have both sufficient potency and acceptable toxicity for clinical investigation. One promising adjuvant is QS-21, a saponin natural product that is the immunopotentiator of choice in many cancer and infectious disease vaccine clinical trials. However, the therapeutic promise of QS-21 adjuvant is curtailed by several factors, including its scarcity, difficulty in purification to homogeneity, dose-limiting toxicity, and chemical instability. Here, we report the design, synthesis, and evaluation of chemically stable synthetic saponins. These novel, amide-modified, non-natural substances exhibit immunopotentiating effects in vivo that rival or exceed that of QS-21 in evaluations with the GD3-KLH melanoma conjugate vaccine. The highly convergent synthetic preparation of these novel saponins establishes new avenues for discovering improved molecular adjuvants for specifically tailored vaccine therapies.

• Authors: Michelle M Adams, Payal Damani, Nicholas R Perl, Annie Won, Feng Hong, Philip O Livingston, Govind Ragupathi, David Y Gin
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 132 Issue 6 Pg. 1939-45 (Feb 17 2010) ISSN: 1520-5126 [Electronic] United States
• PMID: 20088518 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Adjuvants, Immunologic
• Saponins
• Vaccines

Topics

• Adjuvants, Immunologic (chemical synthesis, isolation & purification)
• Animals
• Cell Line, Tumor
• Drug Design
• Female
• Mice
• Mice, Inbred C57BL
• Quillaja (chemistry)
• Saponins (chemical synthesis, immunology, isolation & purification)
• Vaccines (immunology)