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"
Altmetric Score
MSK Authors
  1. Nicholas R Perl
    3 Perl
  2. Feng Hong
    10 Hong
  3. Govindaswami Ragupathi
    133 Ragupathi
  4. David Y Gin
    41 Gin
  5. Payal Damani
    9 Damani
  6. Annie Won
    4 Won
  7. Michelle M Adams
    6 Adams