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Lennart Kenne - One of the best experts on this subject based on the ideXlab platform.
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solid phase extraction nmr studies of chromatographic fractions of saponins from Quillaja saponaria
Analytical Chemistry, 2003Co-Authors: Nils T Nyberg, Herbert Baumann, Lennart KenneAbstract:The saponin mixture QH-B from the tree Quillaja saponaria var. Molina was fractionated by RP-HPLC in several steps. The fractions were analyzed by solid-phase extraction NMR (SPE-NMR), a technique combining the workup by solid-phase extraction with on-line coupling to an NMR flow probe. Together with MALDI-TOF mass spectrometry and comparison with chemical shifts of similar saponins, the structures of both major and minor components in QH-B could be obtained. The procedure described is a simple method to determine the structure of components in a complex mixture. The two major fractions of the mixture were found to contain at least 28 saponins, differing in the carbohydrate substructures. Eight of these have not previously been determined. The 28 saponins formed 14 equilibrium pairs by the migration of an O-acyl group between two adjacent positions on a fucosyl residue.
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Multivariate analysis of NMR spectra for saponins from Quillaja saponaria Molina
Analytica Chimica Acta, 2001Co-Authors: Lars I. Nord, Lennart Kenne, Sven P. JacobssonAbstract:Abstract The bark of the South American tree Quillaja saponaria Molina contains at least 100 different saponin structures. A set of known structures were classified by partial least squares regression-discriminant analysis (PLS-DA) on spectra from 1 H NMR. PLS-DA was found to detect structural variations in the different parts of the saponins, encoded in the spectra. The models obtained were used to classify a test set of known structures. The amount of saponin material used for the NMR spectroscopy was only 200 μg/sample. This means that the outlined method is an interesting tool in the structural analysis of minor saponin components from Quillaja. This non-destructive method could also be applied on and facilitate the analysis of other natural products and metabolites since only minor amounts of sample are needed.
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Novel acetylated triterpenoid saponins in a chromatographic fraction from Quillaja saponaria Molina.
Carbohydrate Research, 2000Co-Authors: Lars I. Nord, Lennart KenneAbstract:Six novel fucose 3-O-acetylated saponins, with a quillaic acid aglycone, were isolated from a bark extract from the Quillaja saponaria Molina tree. In addition, a saponin with a novel aglycone (phytolaccagenic acid) and a novel fatty acyl group [(S)-2-methylbutanoyl] for Quillaja saponins was found. The compounds were characterised using NMR spectroscopy, mass spectrometry and chemical methods.
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structural studies of triterpenoid saponins with new acyl components from Quillaja saponaria molina
Phytochemistry, 2000Co-Authors: Shengjun Guo, Lennart KenneAbstract:Eight new triterpenoid saponins were isolated from a bark extract of Quillaja saponaria Molina by silica and reverse phase chromatography. The saponins were characterized by spectroscopic data and chemical methods as phytolaccagenic acid, 22beta-hydroxy-quillaic acid, and echinocystic acid substituted with different oligosaccharides at C-3 and C-28. The O-4 of the fucosyl residue in the 28-O-oligosaccharide was substituted with either acetyl, (S)-2-methylbutanoyl, or (3S,4S)-3-hydroxy-4-methylhexanoyl groups.
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Characterization of some O-acetylated saponins from Quillaja saponaria Molina
Phytochemistry, 2000Co-Authors: Shengjun Guo, Lennart KenneAbstract:Abstract Sixteen saponins were identified from a bark extract of Quillaja saponaria Molina. The compounds were characterized, using NMR spectroscopy, mass spectrometry and monosaccharide analysis, as quillaic acid substituted at C-3 with oligosaccharides consisting of a disaccharide, β- D -Gal p -(1→2)-β- D -Glc p A substituted with either D -xylose or L -rhamnose and at C-28 with complex oligosaccharide structures consisting of a disaccharide, α- L -Rha p -(1→2)-4- O -acetyl-β- D -Fuc p , substituted with various amount of D -xylose, D -glucose, D -apiose, and L -rhamnose.
Bruce K. Cassels - One of the best experts on this subject based on the ideXlab platform.
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Quillaja saponaria molina
2021Co-Authors: Carla Delporte, Maite Rodriguezdiaz, Bruce K. CasselsAbstract:Quillaja saponaria Mol., Quillajaceae is an endemic Chilean tree known by the vernacular name: “quillay”. Infusions of its leaves and bark are employed traditionally to combat cough and bronchitis. The bark decoction is used to treat chronic skin lesions. Also, the Mapuche people use the bark as an analgesic and as a detergent. The whole aerial parts are one of the main industrial sources of triterpene saponins. Their structures and biosynthesis are quite complex. These saponins are responsible for the biological properties for which they are used in the food, cosmetic and pharmaceutical industries for their surfactant properties. Due to their powerful immunoadjuvant properties, Quillaja saponins are used to manufacture vaccines for human and veterinary use. Together with antigens, cholesterol and phospholipids, they form immunostimulant complexes (ISCOMs) which have proved to be an effective way of presenting antigens to the immune system. Additionally, the analgesic and anti-inflammatory properties of the main aglycone, quillaic acid, have been demonstrated in preclinical models.
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antihyperalgesic activity of quillaic acid obtained from Quillaja saponaria mol
Current Topics in Medicinal Chemistry, 2019Co-Authors: Sylvia Arrau, Carla Delporte, Bruce K. Cassels, Maite Rodriguezdiaz, Gabriela Valenzuelabarra, Andres Barriga, Hugo F. MirandaAbstract:Background Quillaja saponaria Mol. bark contains a high concentration of triterpene saponins that have been used for centuries as a cleansing, antiinflammatory and analgesic agent in Chilean folk medicine. In earlier studies, in mice, both the anti-inflammatory as well as the antinociceptive effect of the major sapogenin, quillaic acid have been demonstrated (QA). Objective To determine the antihyperalgesic effect of QA one and seven days after itpl administration of complete Freund's adjuvant (CFA) in male mice using the hot plate test in the presence of complete Freund's adjuvant (HP/CFA) as an acute and chronic skeletal muscle pain model. Methods The present study evaluated the antihyperalgesic activity of QA against acute and chronic skeletal muscle pain models in mice using the hot plate test in the presence of complete Freund's adjuvant (HP/CFA), at 24 h (acute assay) and 7 days (chronic assay) , with dexketoprofen (DEX) as the reference drug. Results In acute and chronic skeletal muscle pain assays, QA at 30 mg/kg ip elicited its maximal antihyperalgesic effects (65.0% and 53.4%) at 24 h and 7 days, respectively. The maximal effect of DEX (99.0 and 94.1 at 24 h and 7 days, respectively) was induced at 100 mg/kg. Conclusion QA and DEX elicit dose-dependent antihyperalgesic effects against acute and chronic skeletal muscle pain, but QA is more potent than DEX in the early and late periods of inflammatory pain induced by CFA.
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Topical anti-inflammatory activity of quillaic acid from Quillaja saponaria Mol. and some derivatives.
Journal of Pharmacy and Pharmacology, 2011Co-Authors: Maité Rodríguez-díaz, Carla Delporte, Carlos Cartagena, Bruce K. Cassels, Patricia González, Ximena Silva, Fredy León, Ludger A. WessjohannAbstract:Objectives Quillaic acid is the major aglycone of the widely studied saponins of the Chilean indigenous tree Quillaja saponaria Mol. The industrial availability of Quillaja saponins and the extensive functionalisation of this triterpenoid provide unique opportunities for structural modification and pose a challenge from the standpoint of selectivity in regard to one or the other secondary alcohol group, the aldehyde, and the carboxylic acid functions. The anti-inflammatory activity of this sapogenin has not been studied previously and it has never been used to obtain potential anti-inflammatory derivatives. Methods A series of quillaic acid derivatives were prepared and subjected to topical assays for the inhibition of inflammation induced by arachidonic acid or phorbol ester. Key findings Quillaic acid exhibited strong topical anti-inflammatory activity in both models. Most of its derivatives were less potent, but the hydrazone 8 showed similar potency to quillaic acid in the TPA assay. Conclusions The structural modifications performed and the biological results suggest that the aldehyde and carboxyl groups are relevant to the anti-inflammatory activity in these models.
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Antinociceptive activity of Quillaja saponaria Mol. saponin extract, quillaic acid and derivatives in mice
Journal of Ethnopharmacology, 2010Co-Authors: Sylvia Arrau, Maité Rodríguez-díaz, Carla Delporte, Carlos Cartagena, Bruce K. Cassels, Patricia González, Ximena Silva, Hugo F. MirandaAbstract:Abstract Ethnopharmacological relevance Quillaja saponaria bark contains a high percentage of triterpene saponins and has been used for centuries as a cleansing and analgesic agent in Chilean folk medicine. Aim of the study The topical and systemic analgesic effects of a commercial partially purified saponin extract, 3β,16α-dihydroxy-23-oxoolean-12-en-28-oic acid (quillaic acid), methyl 3β,16α-dihydroxy-23-oxoolean-12-en-28-oate and methyl 4-nor-3,16-dioxoolean-12-en-28-oate. Materials and methods The samples were assessed in mice using the topical tail-flick and i.p. hot-plate tests, respectively. Results All the samples showed activity in both analgesic tests in a dose-dependent manner. The most active against tail flick test was commercial partially purified saponin extract (EC50 27.9 mg%, w/v) and more than the ibuprofen sodium. On hot-plate test, methyl 4-nor-3, 16-dioxoolean-12-en-28-oate was the most active (ED50 12.2 mg/kg) and more than the ibuprofen sodium. Conclusions The results of the present study demonstrated that Quillaja saponaria saponins, quillaic acid, its methyl ester, and one of the oxidized derivatives of the latter, elicit dose-dependent antinociceptive effects in two murine thermal models.
Carla Delporte - One of the best experts on this subject based on the ideXlab platform.
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Quillaja saponaria molina
2021Co-Authors: Carla Delporte, Maite Rodriguezdiaz, Bruce K. CasselsAbstract:Quillaja saponaria Mol., Quillajaceae is an endemic Chilean tree known by the vernacular name: “quillay”. Infusions of its leaves and bark are employed traditionally to combat cough and bronchitis. The bark decoction is used to treat chronic skin lesions. Also, the Mapuche people use the bark as an analgesic and as a detergent. The whole aerial parts are one of the main industrial sources of triterpene saponins. Their structures and biosynthesis are quite complex. These saponins are responsible for the biological properties for which they are used in the food, cosmetic and pharmaceutical industries for their surfactant properties. Due to their powerful immunoadjuvant properties, Quillaja saponins are used to manufacture vaccines for human and veterinary use. Together with antigens, cholesterol and phospholipids, they form immunostimulant complexes (ISCOMs) which have proved to be an effective way of presenting antigens to the immune system. Additionally, the analgesic and anti-inflammatory properties of the main aglycone, quillaic acid, have been demonstrated in preclinical models.
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antihyperalgesic activity of quillaic acid obtained from Quillaja saponaria mol
Current Topics in Medicinal Chemistry, 2019Co-Authors: Sylvia Arrau, Carla Delporte, Bruce K. Cassels, Maite Rodriguezdiaz, Gabriela Valenzuelabarra, Andres Barriga, Hugo F. MirandaAbstract:Background Quillaja saponaria Mol. bark contains a high concentration of triterpene saponins that have been used for centuries as a cleansing, antiinflammatory and analgesic agent in Chilean folk medicine. In earlier studies, in mice, both the anti-inflammatory as well as the antinociceptive effect of the major sapogenin, quillaic acid have been demonstrated (QA). Objective To determine the antihyperalgesic effect of QA one and seven days after itpl administration of complete Freund's adjuvant (CFA) in male mice using the hot plate test in the presence of complete Freund's adjuvant (HP/CFA) as an acute and chronic skeletal muscle pain model. Methods The present study evaluated the antihyperalgesic activity of QA against acute and chronic skeletal muscle pain models in mice using the hot plate test in the presence of complete Freund's adjuvant (HP/CFA), at 24 h (acute assay) and 7 days (chronic assay) , with dexketoprofen (DEX) as the reference drug. Results In acute and chronic skeletal muscle pain assays, QA at 30 mg/kg ip elicited its maximal antihyperalgesic effects (65.0% and 53.4%) at 24 h and 7 days, respectively. The maximal effect of DEX (99.0 and 94.1 at 24 h and 7 days, respectively) was induced at 100 mg/kg. Conclusion QA and DEX elicit dose-dependent antihyperalgesic effects against acute and chronic skeletal muscle pain, but QA is more potent than DEX in the early and late periods of inflammatory pain induced by CFA.
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Topical anti-inflammatory activity of quillaic acid from Quillaja saponaria Mol. and some derivatives.
Journal of Pharmacy and Pharmacology, 2011Co-Authors: Maité Rodríguez-díaz, Carla Delporte, Carlos Cartagena, Bruce K. Cassels, Patricia González, Ximena Silva, Fredy León, Ludger A. WessjohannAbstract:Objectives Quillaic acid is the major aglycone of the widely studied saponins of the Chilean indigenous tree Quillaja saponaria Mol. The industrial availability of Quillaja saponins and the extensive functionalisation of this triterpenoid provide unique opportunities for structural modification and pose a challenge from the standpoint of selectivity in regard to one or the other secondary alcohol group, the aldehyde, and the carboxylic acid functions. The anti-inflammatory activity of this sapogenin has not been studied previously and it has never been used to obtain potential anti-inflammatory derivatives. Methods A series of quillaic acid derivatives were prepared and subjected to topical assays for the inhibition of inflammation induced by arachidonic acid or phorbol ester. Key findings Quillaic acid exhibited strong topical anti-inflammatory activity in both models. Most of its derivatives were less potent, but the hydrazone 8 showed similar potency to quillaic acid in the TPA assay. Conclusions The structural modifications performed and the biological results suggest that the aldehyde and carboxyl groups are relevant to the anti-inflammatory activity in these models.
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Antinociceptive activity of Quillaja saponaria Mol. saponin extract, quillaic acid and derivatives in mice
Journal of Ethnopharmacology, 2010Co-Authors: Sylvia Arrau, Maité Rodríguez-díaz, Carla Delporte, Carlos Cartagena, Bruce K. Cassels, Patricia González, Ximena Silva, Hugo F. MirandaAbstract:Abstract Ethnopharmacological relevance Quillaja saponaria bark contains a high percentage of triterpene saponins and has been used for centuries as a cleansing and analgesic agent in Chilean folk medicine. Aim of the study The topical and systemic analgesic effects of a commercial partially purified saponin extract, 3β,16α-dihydroxy-23-oxoolean-12-en-28-oic acid (quillaic acid), methyl 3β,16α-dihydroxy-23-oxoolean-12-en-28-oate and methyl 4-nor-3,16-dioxoolean-12-en-28-oate. Materials and methods The samples were assessed in mice using the topical tail-flick and i.p. hot-plate tests, respectively. Results All the samples showed activity in both analgesic tests in a dose-dependent manner. The most active against tail flick test was commercial partially purified saponin extract (EC50 27.9 mg%, w/v) and more than the ibuprofen sodium. On hot-plate test, methyl 4-nor-3, 16-dioxoolean-12-en-28-oate was the most active (ED50 12.2 mg/kg) and more than the ibuprofen sodium. Conclusions The results of the present study demonstrated that Quillaja saponaria saponins, quillaic acid, its methyl ester, and one of the oxidized derivatives of the latter, elicit dose-dependent antinociceptive effects in two murine thermal models.
Bror Morein - One of the best experts on this subject based on the ideXlab platform.
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effects of carbohydrate modification of Quillaja saponaria molina qh b fraction on adjuvant activity cholesterol binding capacity and toxicity
Vaccine, 1997Co-Authors: Bengt Rönnberg, Makonnen Fekadu, Lennart Kenne, Shahriar Behboudi, Bror MoreinAbstract:Abstract The iscom is an efficient antigen-presenting system for various antigens inducing both MHC class I and class II restricted immune responses. Protective immunity has been evoked against a variety of infectious agents. The saponin adjuvant Quil A, which was originally used to form iscoms, is composed of a mixture of structurally similar triterpenoids from Quillaja saponaria Molina having different biological activities. A purified, toxic Quillaja triterpenoid fraction with strong adjuvant activity, designated QH-B, was used to study whether modification of the carbohydrate moiety with sodium periodate would alter the toxicity without harming adjuvant activity and cholesterol-binding capacity. Most sugars, and in particular Api, Gal and Xyl, were modified by periodate treatment with only minor changes of the molecular weights indicating no loss of sugar residues. The adjuvant activity of QH-B was reduced in a dose-related manner, and at a concentration of 25 mM sodium periodate a significant reduction in toxicity was observed. The differences in both toxicity and adjuvant activity of the periodate-treated QH-B could be derived from alternations in the structure of the sugars Gal and Xyl, while modification of Api may influence adjuvant activity but not toxicity in vivo . The cholesterol-binding capacity, a prerequisite for iscom formation, was not affected by periodate oxidation at the doses tested. However, the use of modified QH-B as described in the present study for iscom-matrix formation resulted in “saponin-lipid complexes” which, to a various degree or totally, deviated from the characteristic iscom morphology.
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IN VIVO AND IN VITRO INDUCTION OF IL-6 BY Quillaja saponaria MOLINA TRITERPENOID FORMULATIONS
Cytokine, 1997Co-Authors: Shahriar Behboudi, Bror Morein, Maria Villacres-erikssonAbstract:Abstract Quillaja saponaria Molina and some of the defined Quillaja components are potent adjuvants. An important function of adjuvants is the activation of antigen-presenting cells (APC), a prerequisite for the development of immune responses. Interleukin 6 (IL-6) has been identified as a key factor in the generation of cytolytic T lymphocytes, which constitute an important effector mechanism elicited by immuno-stimulatory complex (iscom)-borne antigens. To identify factors relevant to the unique property of iscoms to mediate CTL responses, we analysed the capacity of different defined Quillaja triterpenoid components in various formulations to stimulate production of IL-6 by APC in vitro and in vivo. The iscom formed with Quillaja adjuvant and incorporated influenza virus envelope proteins elicited the highest secretion of IL-6. The production of Il-6 was also stimulated by the antigen free matrix of the iscom and even by the Quillaja triterpenoids as free components albeit to a significantly lesser extent. Among the various combinations of QH-A and QH-C tested and also the original semipurified spikoside, the QH 7.0.3 matrix was the most efficient formulation for activation of Il-6 production by APC. In general, an increasing proportion of QH-A vs QH-C increases the capacity to activate APC. The results demonstrate that the incorporated antigen and the adjuvant component in the same particle have the synergistic effects on immunogenicity.
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In vitro activation of antigen-presenting cells (APC) by defined composition of Quillaja saponaria Molina triterpenoids.
Clinical and Experimental Immunology, 1996Co-Authors: Shahriar Behboudi, Bror Morein, Maria Villacres-erikssonAbstract:The capacity of adjuvants to stimulate cytokine production by APC is important for the initiation of the immune response. Novel adjuvant formulations based on the iscom technology have been developed using selected triterpenoid components from Quillaja saponaria Molina. Five of these new Quillaja formulations were used to prepare matrix (an antigen-free particle) and tested for their capacity to stimulate IL-1 secretion by murine peritoneal cells in vitro. The formulation denominated QH 7.0.3 was superior to the other matrix formulations, including the original spikoside matrix. The QH 7.0.3 formulation in iscoms containing influenza virus envelope antigens induced IL-1 secretion more efficiently than the antigen-free matrix, or a mixture of matrix and viral antigens, or the free Quillaja components of similar composition. Compared with adjuvants known as IL-1 inducers, QH 7.0.3 flu-iscoms were as efficient as the most prominent IL-1 inducer, i.e. lipopolysaccharide (LPS) and superior to cholera toxin (CT) and muramyl dipeptide (MDP). These results indicate that the composition per se of triterpenoids included in iscoms or matrix has a prominent influence on the level of APC activation which may result in qualitatively different immune responses in vivo.
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adjuvant activity of non toxic Quillaja saponaria molina components for use in iscom matrix
Vaccine, 1995Co-Authors: Bengt Rönnberg, Makonnen Fekadu, Bror MoreinAbstract:It is well established that ISCOMs function efficiently as an antigen-presenting system and protective immunity has been evoked against a variety of infectious agents. The built-in saponin adjuvant from Quillaja saponaria Molina is responsible for the strong immunoenhancing activity displayed by the ISCOM. However, to allow the use of ISCOMs in human vaccines it is necessary to determine the immunological properties and toxicity of chemically defined Quillaja components. Thus, the present study was carried out in a mouse model to determine the adjuvant activity and toxicity of "free", isolated Quillaja components, as well as formulated into particles, i.e. ISCOM matrix. The purified Quillaja components and the ISCOM matrix formulations were examined for their adjuvant activity in a model system consisting of purified influenza virus antigen and Quillaja saponins. It was demonstrated that a Quillaja component, designated QH-C, either as a "free" component or in an ISCOM matrix, has a strong adjuvant activity, but little or no toxicity in the doses tested. In addition, QH-C in the form of ISCOM matrix does not induce any local reactions at the site of injection. Thus, ISCOMs containing the QH-C component, devoid of toxicity, but with strong adjuvant activity, can prove to be useful in adjuvant formulations for human use.
Bengt Rönnberg - One of the best experts on this subject based on the ideXlab platform.
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Triterpenoid saponins containing an acetylated branched D-fucosyl residue from Quillaja saponaria Molina.
Phytochemistry, 2000Co-Authors: Shengjun Guo, Bengt Rönnberg, Lennart Kenne, Elisabet Falk, Bo G SundquistAbstract:Seven novel saponins were isolated from a bark extract of Quillaja saponaria Molina. the compounds were characterized, using mainly NMR spectroscopy, mass spectrometry and chemical methods, as quillaic acid substituted at C-3 with oligosaccharides consisting of various compositions of D-glucuronic acid D-galactose, D-xylose, and L-rhamnose and at C-28 with complex oligosaccharide structures consisting of various compositions of D-xylose, L-rhamnose, D-apiose and a branched 4-O-acetyl-D-fucose residue.
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separation and structural analysis of some saponins from Quillaja saponaria molina
Carbohydrate Research, 1999Co-Authors: Nils T Nyberg, Bengt Rönnberg, Lennart Kenne, Bo G SundquistAbstract:A fraction of saponins from Quillaja saponaria Molina, QH-B, was fractionated by consecutive separations on three different reverse-phase HPLC systems. Eight compounds were isolated and the structures of these were elucidated mainly by sugar analysis and NMR spectroscopy. The structures consisted of a quillaic acid substituted with two different trisaccharides at C-3, beta-D-Galp-(1-->2)-[alpha-L-Rhap-(1-->3)]-beta-D-GlcpA and beta-D-Galp-(1-->2)-[beta-D-Xylp-(1-->3)]-beta-D-GlcpA, and a tetra- or pentasaccharide at C-28, beta-D-Xylp-(1-->4)-[beta-D-Glcp-(1-->3)]-alpha-L-Rhap-(1--> 2)-beta-D-Fucp and beta-D-Apif-(1-->3)-beta-D-Xylp-(1-->4)-[beta-D-Glcp-(1-->3) ]-alpha-L- Rhap-(1-->2)-beta-D-Fucp. These compounds were further substituted with an acyl group either at O-3 or O-4 of the fucose residue, which is the sugar linked to C-28 of the quillaic acid.
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triterpenoid saponins from Quillaja saponaria
Phytochemistry, 1998Co-Authors: Shengjun Guo, Bengt Rönnberg, Lennart Kenne, Lennart N Lundgren, Bo G SundquistAbstract:Three new saponins were isolated from a commercial bark extract of Quillaja saponaria Molina. These compounds were also obtained as degradation products from larger saponins in this extract when treated with strong alkali. The compounds were characterized, using mainly NMR spectroscopy, mass spectrometry and chemical methods, as quillaic acid 3-O-?beta-D-galactopyranosyl-(1-->2)-beta-D-glucopyranosiduronic acid?, 3-O-?alpha-L-rhamnopyranosyl-(1-->3)-[beta-D-galactopyranosyl-(1-->2)] -beta-D-glucopyranosiduronic acid? and 3-O-?beta-D-xylopyranosyl-(1-->3)-[beta-D-galactopyranosyl -(1-->2)]-beta-D-glucopyranosiduronic acid?, respectively.
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effects of carbohydrate modification of Quillaja saponaria molina qh b fraction on adjuvant activity cholesterol binding capacity and toxicity
Vaccine, 1997Co-Authors: Bengt Rönnberg, Makonnen Fekadu, Lennart Kenne, Shahriar Behboudi, Bror MoreinAbstract:Abstract The iscom is an efficient antigen-presenting system for various antigens inducing both MHC class I and class II restricted immune responses. Protective immunity has been evoked against a variety of infectious agents. The saponin adjuvant Quil A, which was originally used to form iscoms, is composed of a mixture of structurally similar triterpenoids from Quillaja saponaria Molina having different biological activities. A purified, toxic Quillaja triterpenoid fraction with strong adjuvant activity, designated QH-B, was used to study whether modification of the carbohydrate moiety with sodium periodate would alter the toxicity without harming adjuvant activity and cholesterol-binding capacity. Most sugars, and in particular Api, Gal and Xyl, were modified by periodate treatment with only minor changes of the molecular weights indicating no loss of sugar residues. The adjuvant activity of QH-B was reduced in a dose-related manner, and at a concentration of 25 mM sodium periodate a significant reduction in toxicity was observed. The differences in both toxicity and adjuvant activity of the periodate-treated QH-B could be derived from alternations in the structure of the sugars Gal and Xyl, while modification of Api may influence adjuvant activity but not toxicity in vivo . The cholesterol-binding capacity, a prerequisite for iscom formation, was not affected by periodate oxidation at the doses tested. However, the use of modified QH-B as described in the present study for iscom-matrix formation resulted in “saponin-lipid complexes” which, to a various degree or totally, deviated from the characteristic iscom morphology.
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adjuvant activity of non toxic Quillaja saponaria molina components for use in iscom matrix
Vaccine, 1995Co-Authors: Bengt Rönnberg, Makonnen Fekadu, Bror MoreinAbstract:It is well established that ISCOMs function efficiently as an antigen-presenting system and protective immunity has been evoked against a variety of infectious agents. The built-in saponin adjuvant from Quillaja saponaria Molina is responsible for the strong immunoenhancing activity displayed by the ISCOM. However, to allow the use of ISCOMs in human vaccines it is necessary to determine the immunological properties and toxicity of chemically defined Quillaja components. Thus, the present study was carried out in a mouse model to determine the adjuvant activity and toxicity of "free", isolated Quillaja components, as well as formulated into particles, i.e. ISCOM matrix. The purified Quillaja components and the ISCOM matrix formulations were examined for their adjuvant activity in a model system consisting of purified influenza virus antigen and Quillaja saponins. It was demonstrated that a Quillaja component, designated QH-C, either as a "free" component or in an ISCOM matrix, has a strong adjuvant activity, but little or no toxicity in the doses tested. In addition, QH-C in the form of ISCOM matrix does not induce any local reactions at the site of injection. Thus, ISCOMs containing the QH-C component, devoid of toxicity, but with strong adjuvant activity, can prove to be useful in adjuvant formulations for human use.
