Design and synthesis of potent Quillaja saponin vaccine adjuvants Journal Article
| Authors: | Adams, M. M.; Damani, P.; Perl, N. R.; Won, A.; Hong, F.; Livingston, P. O.; Ragupathi, G.; Gin, D. Y. |
| Article Title: | 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. © 2010 American Chemical Society. |
| Keywords: | controlled study; unclassified drug; clinical trial; nonhuman; mouse; animals; mice; melanoma; animal experiment; in vivo study; drug potency; drug effect; cell line, tumor; drug design; drug synthesis; mice, inbred c57bl; immune response; cancer vaccine; in-vivo; chemical structure; immunostimulation; toxicity; adjuvants, immunologic; drug conjugation; anti-tumors; vaccines; saponins; amides; clinical investigation; qs 21; adjuvant; conjugate vaccine; anti-viral vaccine; chemical instability; dose limiting toxicity; infectious disease; natural products; synthetic preparation; gd3 klh antigen; saponin; quillaja |
| Journal Title: | Journal of the American Chemical Society |
| Volume: | 132 |
| Issue: | 6 |
| ISSN: | 0002-7863 |
| Publisher: | American Chemical Society |
| Date Published: | 2010-02-17 |
| Start Page: | 1939 |
| End Page: | 1945 |
| Language: | English |
| DOI: | 10.1021/ja9082842 |
| PUBMED: | 20088518 |
| PROVIDER: | scopus |
| PMCID: | PMC2820154 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 4" - "Export Date: 20 April 2011" - "CODEN: JACSA" - "Source: Scopus" |
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