Preclinical evaluation of the synthetic adjuvant SQS-21 and its constituent isomeric saponins Journal Article

Authors: Ragupathi, G.; Damani, P.; Deng, K.; Adams, M. M.; Hang, J.; George, C.; Livingston, P. O.; Gin, D. Y.
Article Title: Preclinical evaluation of the synthetic adjuvant SQS-21 and its constituent isomeric saponins
Abstract: The saponin fraction QS-21 from Quillaja saponaria has been demonstrated to be a potent immunological adjuvant when mixed with keyhole limpet hemocyanin conjugate vaccines, as well as with other classes of subunit antigen vaccines. QS-21 adjuvant is composed of two isomers that include the apiose and xylose forms in a ratio of 65:35, respectively. The chemical syntheses of these two isomers in pure form have recently been disclosed. Herein we describe detailed in vivo immunological evaluations of these synthetic QS-21 isomeric constituents, employing the GD3-KLH melanoma antigen. With this vaccine construct, high antibody titers against GD3 ganglioside and KLH were elicited when GD3-KLH was co-administered with adjuvant, either as the individual separate synthetic QS-21 isomers (SQS-21-Api or SQS-21-Xyl), or as its reconstituted 65:35 isomeric mixture (SQS-21). These antibody titer levels were comparable to that elicited by vaccinations employing naturally derived QS-21 (PQS-21). Moreover, toxicities of the synthetic saponin adjuvants were also found to be comparable to that of naturally derived PQS-21. These findings demonstrate unequivocally that the adjuvant activity of QS-21 resides in these two principal isomeric forms, and not in trace contaminants within the natural extracts. This lays the foundation for future exploration of structure-function correlations to enable the discovery of novel saponins with increased potency, enhanced stability, and attenuated toxicity. © 2010 Elsevier Ltd. All rights reserved.
Keywords: controlled study; unclassified drug; human cell; drug activity; nonhuman; flow cytometry; mouse; animals; mice; melanoma; animal experiment; weight reduction; in vivo study; cancer cell culture; drug structure; drug screening; drug evaluation, preclinical; mice, inbred c57bl; immune response; cancer vaccines; immunogenicity; antibody response; vaccination; toxicity testing; immunological adjuvant; melanoma antigen; molecular structure; plant extract; adjuvants, immunologic; structure analysis; synthesis; antibody formation; antibody titer; hemocyanin; saponins; gangliosides; quillaja; melanoma vaccine; conjugate vaccines; saponin adjuvant; synthetic adjuvant; ganglioside gd3 keyhole limpet hemocyanin conjugate; quillaja saponaria extract; saponin derivative; isomer; quillaja saponaria
Journal Title: Vaccine
Volume: 28
Issue: 26
ISSN: 0264-410X
Publisher: Elsevier Inc.  
Date Published: 2010-06-11
Start Page: 4260
End Page: 4267
Language: English
DOI: 10.1016/j.vaccine.2010.04.034
PUBMED: 20450868
PROVIDER: scopus
PMCID: PMC2882175
Notes: --- - "Export Date: 20 April 2011" - "CODEN: VACCD" - "Source: Scopus"
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MSK Authors
  1. Jianfeng Hang
    3 Hang
  2. Kai Deng
    6 Deng
  3. Govindaswami Ragupathi
    133 Ragupathi
  4. David Y Gin
    41 Gin
  5. Payal Damani
    9 Damani
  6. Michelle M Adams
    6 Adams
  7. Constantine M George
    10 George