Design, synthesis, and immunologic evaluation of vaccine adjuvant conjugates based on QS-21 and tucaresol Journal Article


Authors: Fernandez- Tejada, A.; Chea, E. K.; George, C.; Gardner, J. R.; Livingston, P. O.; Ragupathi, G.; Tan, D. S.; Gin, D. Y.
Article Title: Design, synthesis, and immunologic evaluation of vaccine adjuvant conjugates based on QS-21 and tucaresol
Abstract: Immunoadjuvants are used to potentiate the activity of modern subunit vaccines that are based on molecular antigens. An emerging approach involves the combination of multiple adjuvants in a single formulation to achieve optimal vaccine efficacy. Herein, to investigate such potential synergies, we synthesized novel adjuvant conjugates based on the saponin natural product QS-21 and the aldehyde tucaresol via chemoselective acylation of an amine at the terminus of the acyl chain domain in QS saponin variants. In a preclinical mouse vaccination model, these QS saponin-tucaresol conjugates induced antibody responses similar to or slightly higher than those generated with related QS saponin variants lacking the tucaresol motif. The conjugates retained potent adjuvant activity, low toxicity, and improved activity-toxicity profiles relative to QS-21 itself and induced IgG subclass profiles similar to those of QS-21, indicative of both Th1 cellular and Th2 humoral immune responses. This study opens the door to installation of other substituents at the terminus of the acyl chain domain to develop additional QS saponin conjugates with desirable immunologic properties.
Keywords: carrier protein; unclassified drug; drug activity; drug efficacy; drug potentiation; nonhuman; mouse; animal experiment; drug potency; drug structure; drug screening; drug design; drug synthesis; immunoreactivity; th2 cell; amine; cellular immunity; antigen; immunoglobulin g; antibody response; vaccination; immunological adjuvant; drug toxicity; mucin 1; th1 cell; natural product; humoral immunity; vaccine; carbohydrates; drug formulation; subunit vaccine; acylation; qs 21; mouse model; saponin; aldehyde; saponin derivative; qs-21; ovalbumin; female; article; immunoadjuvant; saponin conjugate; tucaresol; aryl iodide saponin; muc1 klh; saponin tucaresol adjuvant conjugate; vaccine aduvant conjugate
Journal Title: Bioorganic & Medicinal Chemistry
Volume: 22
Issue: 21
ISSN: 0968-0896
Publisher: Pergamon-Elsevier Science Ltd  
Date Published: 2014-11-01
Start Page: 5917
End Page: 5923
Language: English
DOI: 10.1016/j.bmc.2014.09.016
PROVIDER: scopus
PUBMED: 25284254
PMCID: PMC4410046
DOI/URL:
Notes: Export Date: 1 December 2014 -- Source: Scopus
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MSK Authors
  1. Govindaswami Ragupathi
    133 Ragupathi
  2. Derek S Tan
    69 Tan
  3. David Y Gin
    41 Gin
  4. Jeffrey Gardner
    33 Gardner
  5. Constantine M George
    10 George
  6. Eric   Chea
    3 Chea