title: Altered immunomodulating and toxicological properties of degraded Quillaja saponaria Molina saponins.
abstract: Quillaja saponins are readily hydrolyzed under physiological conditions, yielding deacylated forms that are significantly less toxic than their precursors. Yet, deacylated saponins are unable to stimulate a strong primary immune response. Although deacylated saponins elicit a strong total IgG response, their capacity to stimulate a Thl type IgG isotype profile (i.e. high levels of IgG2a and IgG2b) has been significantly diminished. Instead, an IgG profile closer to that of a Th2 immune response is stimulated (i.e. high IgG1 levels). Deacylated saponins have also lost their capacity to elicit an effective T cell immunity, as shown by their stimulation of a marginal lymphoproliferative response and their inability to elicit the production of cytotoxic lymphocytes (CTL). Modification of the immune-modulating properties brought by the degradation of quillaja saponins during vaccine storage may change the intended immune response from a Th1 to a Th2 type. This alteration would have negligible effects on vaccines depending on Th2 immunity mediated by neutralizing antibodies. However, the performance of vaccines directed against intracellular pathogens as well as therapeutic cancer vaccines may be seriously affected by the loss of their capacity to stimulate both a Th1 immune response and the production of CTL.
authors.affiliation: Galenica Pharmaceuticals, Inc., Frederick, MD 21701, USA. dmarciani@galenicapharma.com
authors.forename: D J
authors.initials: DJ
authors.lastname: Marciani
authors.forename: A K
authors.initials: AK
authors.lastname: Pathak
authors.forename: R C
authors.initials: RC
authors.lastname: Reynolds
authors.forename: L
authors.initials: L
authors.lastname: Seitz
authors.forename: R D
authors.initials: RD
authors.lastname: May
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D051379:Mice; D008810:Mice, Inbred C57BL; D009828:Oleanolic Acid / Q000031:analogs & derivatives*; D010047:Ovalbumin / Q000276:immunology; D012502:Sapogenins / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage*
chemical_list: D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D012502:Sapogenins; D014612:Vaccines; C005564:quillaic acid; D009828:Oleanolic Acid; D010047:Ovalbumin