Preclinical evaluation of the synthetic adjuvant SQS-21 and its constituent isomeric saponins.
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.
Ragupathi
Govind
G
Laboratory of Tumor Vaccinology, Melanoma and Sarcoma Service, Department of Medicine, 1275 York Avenue, New York, NY 10065, USA. ragupatg@mskcc.org
Damani
Payal
P
Deng
Kai
K
Adams
Michelle M
MM
Hang
Jianfeng
J
George
Constantine
C
Livingston
Philip O
PO
Gin
David Y
DY
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation; D019496:Cancer Vaccines / Q000276:immunology; D004353:Drug Evaluation, Preclinical; D005260:Female; D005732:Gangliosides / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D008545:Melanoma / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D012503:Saponins / Q000138:chemical synthesis / Q000276:immunology*
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D005732:Gangliosides; D012503:Saponins; C078785:saponin QA-21V1; C026226:ganglioside, GD3; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin
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