Fractionation, structural studies, and immunological characterization of the semi-synthetic Quillaja saponins derivative GPI-0100.
Unfractionated GPI-0100 (UFGPI-0100) containing semi-synthetic derivatives of deacylated Quillaja saponins (DS saponins) modified at the glucuronic acid residue was resolved by reverse phase low-pressure liquid chromatography (RP-LPLC) into two fractions, RP18-1 and RP18-2, with different compositions and adjuvanticity. The fraction RP18-1 contained DS saponin adducts of N-dicyclohexylurea, and stimulated Th2 immunity with production of IgG1, while the RP18-2 fraction contained the dodecylamide derivatives of DS saponins and stimulated Th1 immunity with production of IgG2a, IFN-gamma, IL-2, and CTL. The strong immune stimulatory properties of RP18-2, relative to RP18-1, and the formation of RP18-1/RP18-2 mixed micelles may account for the effective stimulation of Th1 immunity by UFGPI-0100. UFGPI-0100 was free of acylated quillaja saponin components, including the more stable QS-7.
Marciani
Dante J
DJ
Galenica Pharmaceuticals Inc., 2800 Milan Court, Suite 118, Birmingham, AL 35211, USA. marciani.gpi@att.net
Reynolds
Robert C
RC
Pathak
Ashish K
AK
Finley-Woodman
Kyra
K
May
Richard D
RD
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000534:Alum Compounds; D000818:Animals; D000941:Antigens / Q000276:immunology; D002240:Carbohydrate Sequence; D002460:Cell Line; D002853:Chromatography, Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000096:biosynthesis; D007202:Indicators and Reagents; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D013058:Mass Spectrometry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology; D031990:Quillaja / Q000737:chemistry*; D012503:Saponins / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D018417:Th1 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000941:Antigens; D007074:Immunoglobulin G; D007202:Indicators and Reagents; D007376:Interleukin-2; D012503:Saponins; C041524:aluminum sulfate; D007371:Interferon-gamma; D010047:Ovalbumin