Adjuvant activity of non-toxic Quillaja saponaria Molina components for use in ISCOM matrix

Rönnberg, Bengt; Fekadu, Makonnen; Morein, Brør

doi:10.1016/0264-410x(95)00105-a

Cited by 128 publications

(73 citation statements)

References 15 publications

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“…The saponin Quil A, an aqueous extract from the bark of Quillaja saponaria and extracts, mainly QS-21, have been studied as alternatives to alum when strong cell-mediated responses are required [13,14]. In addition to pain on injection, severe local reactions and granulomas, toxicity includes severe haemolysis [5,[15][16][17] making such adjuvants unsuitable for human uses other than for life threatening diseases, such as HIV infection or cancer [18].…”

Section: Alternative Human Adjuvantsmentioning

confidence: 99%

Novel human polysaccharide adjuvants with dual Th1 and Th2 potentiating activity

Petrovsky

2006

Vaccine

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Pure soluble, recombinant and synthetic antigens, despite their better tolerability, are unfortunately often much less immunogenic than live or killed whole organism vaccines. Thus, the move towards the development of safer subunit vaccines has created a major need for more potent adjuvants. In particular, there is an urgent need for adjuvants capable of boosting cellular (Th1) immunity but without unacceptable toxicity. The adjuvant activity of aluminium compounds (aluminium phosphate or hydroxide) was first described by Glenny and colleagues in 1926. Surprisingly, despite the description of over one hundred adjuvants in the scientific literature, alum remains the only adjuvant approved for human use in the USA. Unfortunately, alum has no effect on cellular immunity and is faced with increasing concerns regarding potential for cumulative aluminium toxicity. Why then has alum not been replaced in human vaccines? Despite the enormous number of candidates, potency has invariably been associated with increased toxicity, and this more than anything else has precluded their use, particularly in prophylactic vaccines where safety issues are paramount. Hence, there is a major unmet need for a safe efficacious adjuvant capable of boosting cellular plus humoral immunity. The extensive data on inulin-based adjuvants indicate that these are excellent candidates to replace alum as the adjuvant of choice for many vaccines. Particular advantages offered by inulin-based adjuvants is that they induce cellular in addition to humoral immunity and offer excellent safety, tolerability, ease of manufacture and formulation. Thus, adjuvants based on inulin have enormous potential for use in vaccines against both pathogens and cancer.

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Section: Alternative Human Adjuvantsmentioning

confidence: 99%

Novel human polysaccharide adjuvants with dual Th1 and Th2 potentiating activity

Petrovsky

2006

Vaccine

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“…Rönnberg et al [26] further examined the characteristics of different Quil A fractions in their free form and when formed into Iscom Matrix. Three fractions of Quil A were isolated by reversed-phase high-performance liquid chromatography (RP-HPLC) corresponding to a series of fractions eluting early (QH-A) and a series of the more hydrophobic fractions termed QH-B and QH-C that eluted later.…”

Section: Recent Modifications To Iscomsmentioning

confidence: 99%

“…When adjuvant activity was examined with the purifed saponin fractions in their free form, QH-B promoted greater antibody responses to influenza protein than QH-C followed by QH-A. However, when the fractions (or combinations of the fractions) were administered as Iscom Matrix there was little difference in the antibody responses to influenza proteins [26]. A combination of seven parts QH-A, zero parts QH-B, and three parts QH-C (ISCOPREP 703) has successfully completed various pre-clinical studies and is the basis of ISCOMs and Iscom Matrix vaccines that have been tested in phase I and II human clinical studies [4].…”

Section: Recent Modifications To Iscomsmentioning

confidence: 99%

“…Using the purified saponin fractions QH-A, QH-B, and QH-C, Rönnberg et al [26] found that Iscom Matrix containing various ratios of the three fractions, and even ISCOMs made from Quil A, did not cause significant hemolysis of chicken red blood cells (CRBC) in vitro at levels up to 100 µg/mL. Extensive hemolysis was obtained when free Quil A or QH-B and QH-C were used without being incorporated into ISCOMs or Iscom Matrix.…”

Section: Toxicity Of Saponins Iscoms and Iscom Matrixmentioning

confidence: 99%

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ISCOMs: an adjuvant with multiple functions

Sjölander

Cox

Barr

1998

Journal of Leukocyte Biology

155

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“…Triterpenoid products from Q. saponaria Molina such as QS-21 [21], QH-A, QH-B and QH-C [22] have been defined in the search for effective non-toxic adjuvants suitable for human use. With regard to the products QH-A, QH-B and QH-C, QH-A has low adjuvant activity as measured by the antibody response, a low cell lytic effect in vitro and a prominent capacity to form the cagelike structure of iscoms.…”

Section: Introductionmentioning

confidence: 99%

In vitro activation of antigen-presenting cells (APC) by defined composition of Quillaja saponaria Molina triterpenoids

Behboudi

Morein

Villacrés-Eriksson

1996

Clinical and Experimental Immunology

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SUMMARYThe 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 fluiscoms were as efficient as the most prominent IL-1 inducer, i.e. lipopolysaccaride (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

Cited by 128 publications

References 15 publications

Novel human polysaccharide adjuvants with dual Th1 and Th2 potentiating activity

Novel human polysaccharide adjuvants with dual Th1 and Th2 potentiating activity

ISCOMs: an adjuvant with multiple functions

In vitro activation of antigen-presenting cells (APC) by defined composition of Quillaja saponaria Molina triterpenoids

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