Quillaja

QS-21 is one of the most promising new adjuvants for immune response potentiation and dose-sparing in vaccine therapy given its exceedingly high level of potency and its favorable toxicity profile. Melanoma, breast cancer, small cell lung cancer, prostate cancer, HIV-1, and malaria are among the numerous maladies targeted in more than 80 recent and ongoing vaccine therapy clinical trials involving QS-21 as a critical adjuvant component for immune response augmentation. QS-21 is a natural product immunostimulatory adjuvant, eliciting both T-cell- and antibody-mediated immune responses with microgram doses. Herein is reported the synthesis of QS-21Aapi in a highly modular strategy, applying novel glycosylation methodologies to a convergent construction of the potent saponin immunostimulant. The chemical synthesis of QS-21 offers unique opportunities to probe its mode of biological action through the preparation of otherwise unattainable nonnatural saponin analogues.

Common carp were fed diets containing various levels of Quillaja saponins (QS) (0, 150, 300 and 450 mg kg 1 dry diet) in a completely computerized respirometric system for 4 weeks. Fish fed diets containing QS exhibited significantly higher ABW and specific growth rate than did those fed the control diet; those fed diets containing QS 150 grew fastest but were not significantly different from those fed diets with QS 300 and QS 00450. All the utilization efficiency indices, namely food conversion efficiency (FCE), protein productive value and PG were increased by QS supplementation. There were no significant differences in the average routine metabolic rate between treatments, indicating that dietary QS at the levels tested were not toxic to the carp. Increases in amylase and trypsin specific activities were observed at QS 300 and QS 450. Enzymes of carbohydrate metabolism such as G6PDH, 6-phosphogluconate dehydrogenase and pyruvate kinase were not significantly affected by dietary QS. Activities of the aerobic enzyme Cox and to a limited
extent that of the anaerobic enzyme lactate dehydrogenase were significantly increased by dietary QS but the net effect was a shift towards aerobic metabolism, indicating absence of stress and favouring the anabolic processes. Thus, Quillaja saponin was beneficial as a feed supplement in the common carp.

The adjuvant of the FML-vaccine against murine and canine visceral leishmaniasis, the Riedel de Haen saponin mixture, was fractionated by ion exchange chromatography on DEAE-cellulose to afford one TLC homogeneous Quillaja saponaria Molina QS21 saponin fraction (18.0%), a mixture of two deacylsaponins (19.4%), sucrose (39.9%), sucrose and glucose (19.7%), rutin (0.8%) and quercetin (2.2%), that were identified by comparison of 1H and 13C NMR spectroscopy. The QS21 shows the typical aldehyde group in C-23 (65% equatorial) and a normonoterpene moiety acylated in C-28. The deacylsaponins show the aldehyde group but do not have the normonoterpene moiety. Balb/c mice were vaccinated with 150 μg of FML antigen of Leishmania donovani and 100 μg of each obtained fraction and further challenged by infection with 108 amastigotes of Leishmania chagasi. The safety analysis and the effect on humoral and cellular immune responses and in clinical signs showed that the QS21 saponin and the deacylsaponins are the most active adjuvant compounds of the Riedel the Haen saponin mixture. Both induced the highest and non-significantly different increases in DTH, CD4+ T lymphocytes in spleen, IFN-γ in vitro, body weight gain and the most pronounced reduction of parasite burden in liver (95% for QS21 and 86% for deacylsaponins; p > 0.05). While the QS21 showed mild toxicity, significant adjuvant effect on the anti-FML humoral response before and after infection, and decrease in liver relative weight, the deacylsaponins showed no toxicity, less haemolysis and antibody and DTH responses increased mainly after infection, still inducing a stronger Leishmania-specific in vitro splenocyte proliferation. Our results confirm in the Riedel de Haen saponin extract the presence of deacylsaponins normonoterpene-deprivated which are non-toxic and capable of inducing a specific and strong immunoprotective response in vaccination against murine visceral leishmaniasis.

Quillaja brasiliensis (St. A.-Hil. & Tul.) Mart. es un árbol de ambiente templado, existente en el sur de Brasil, Uruguay, Argentina y Paraguay. Con gran contenido de saponina; tiene propiedades relevantes para la industria, tal como Quillaja saponaria, que se distribuye naturalmente en la región central de Chile. El objetivo de este trabajo es explorar la predicción de áreas con condiciones ambientales disponibles para la presencia de Q. brasiliensis usando un algoritmo de máxima entropía y hacer consideraciones acerca de la historia de la distribución de Q. brasiliensis y Q. saponaria en América del Sur. Los resultados demuestran que las especies de Quillaja son vicariantes climáticas que tuvieron su diferenciación iniciada entre el Mioceno y el Plioceno entre 23-5 millones de años, acompañando los movimientos que diferenciaron a Myrceugenia y otras especies de clima templado, compartiendo con estas especies una historia de migraciones y a través de los cambios ambientales ocurridos durante el Cenozoico reciente.

The chemical characterization of aqueous extracts (AE) of barks, leaves and branches and the saponin fraction denominated QB-90 obtained from Quillaja brasiliensis, a native species from Southern Brazil, show remarkable similarities to Quillaja saponaria saponins which are known as adjuvants in vaccine formulations. In vivo toxicity assays of AE and QB-90 showed not to be lethal for mice in doses ranging from 50 to 1600 microg and 50-400 microg, respectively. Experimental vaccines prepared with bovine herpesvirus type 1 (BHV-1) antigen and either AE (barks 100 microg, leaves 400 microg, branches 400 microg) or QB-90 (100 microg) were able to enhance the immune responses of mice in a comparable manner to saponins from Q. saponaria (QuilA, 100 microg). BHV-1 specific IgG, IgG1 and IgG2a antibody levels in serum were also significantly enhanced by AE, QB-90 and QuilA compared to control group (p<0.05). These results showed that AE and QB-90 from Q. brasiliensis are potential candida...