Structural and Immunological Characterization of the Vaccine Adjuvant QS-21

Kensil, Charlotte R.; Wu, Jiayan; Soltysik, Sean

doi:10.1007/978-1-4615-1823-5_22

Cited by 115 publications

(83 citation statements)

References 27 publications

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“…Thus, this may be the dominant feature of QS21, even in the presence of MPL in the formulation. It has been established that QS21 enhances IgG2a production [31], and our data suggested that the adjuvant can mediate IgG2a responses in the absence of IL-6 and without a compensatory increase in IFN-γ response. A direct stimulatory effect of QS21 on B cells remains to be established.…”

Section: Discussionsupporting

confidence: 59%

“…Montanide ISA720, a metabolizable oil adjuvant (Seppic Inc. Fairfield, NJ) [29]; MF59, squalene/oil emulsion (Chiron Corp. Emeryville, CA) [30]; QS21, a saponin derivative (Antigenics Inc. Lexington, MA) [31]; MPL (from E. coli F583 Rd mutant, Sigma-Aldrich, St Louis, MO); MPL-AF, monophosphoryl lipid A in aqueous formulation (Corixa Inc. Seattle, WA) [32]; MPL-SE, monophosphoryl lipid A in squalene emulsion (Corixa Inc. Seattle WA) [33]; and Freund's Adjuvants, CFA/IFA (Gibco, Grand Island, NY). Additional formulations comprised of combinations of above adjuvants were also used, ISA720/MPL, ISA720/QS21, ISA720/QS21/MPL.…”

Section: Adjuvant Formulationsmentioning

confidence: 99%

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Interleukin-6 has differential influence on the ability of adjuvant formulations to potentiate antibody reponses to a Plasmodium falciparum blood-stage vaccine

Hui

Hashimoto

2007

Vaccine

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The efficacy of vaccine adjuvants can be influenced by the immunological environment of the host, depending on the mechanism(s) by which they exert their immunopotentiating activities. Interleukin-6 is a pleiotropic cytokine that has a broad range of biological activities on immune and non-immune cells. We investigated the role of IL-6 on the ability of nine adjuvant formulations to induce antibody responses to the P. falciparum MSP1-19 malaria vaccine, using IL-6 -/-(KO) mice. Results showed that some adjuvants, ie. MPL-SE, CFA/IFA, ISA720/QS21/MPL, depended on IL-6 for their efficacy, while others exhibited increased potency in its absence. The efficacy of adjuvants in the IL-6 KO environment cannot be solely attributed to their ability to stimulate antigen-specific cellular responses, suggesting that other biological activities of IL-6 are also important. The results further suggest that two adjuvants utilized dissimilar pathways to potentiate the same type of immune response.

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Section: Discussionsupporting

confidence: 59%

Section: Adjuvant Formulationsmentioning

confidence: 99%

Interleukin-6 has differential influence on the ability of adjuvant formulations to potentiate antibody reponses to a Plasmodium falciparum blood-stage vaccine

Hui

Hashimoto

2007

Vaccine

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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]. Muramyl dipeptide (MDP) [19] and other derivatives from Gram-negative bacteria, such as lipopolysaccharides (LPS) and monophosphoryl lipid A [20] have also been used as human adjuvants although toxicity remains the single biggest barrier to the use of such adjuvants for human prophylactic vaccines.…”

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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“…The ability to retain potency to induce IL-4 response in STAT6 KO mice by ISA720 and by QS21 was lost in the ISA720/QS21 formulation. The amphiphilic or surfactant nature of QS21 [34] may have significantly influenced the overall characteristic of the emulsion formulation, which may in turn contributed to the observed changes in adjuvanticity. Since we have previously demonstrated the unique characteristics of adjuvant combinations with liposomes, MDP and MPL [18], the distinctive nature of adjuvant combinations may be a general phenomenon.…”

Section: Discussionmentioning

confidence: 99%

“…Montanide ISA720, a metabolizable oil adjuvant (Seppic Inc. Fairfield, NJ) [32]; MF59, squalene/oil emulsion (Chiron Corp. Emeryville, CA) [33]; QS21, a saponin derivative (Antigenics Inc. Lexington, MA) [34]; MPL (from E. coli F583 Rd mutant, Sigma-Aldrich, St Louis, MO); MPL-AF, monophosphoryl lipid A in aqueous formulation (Corixa Inc. Seattle, WA) [35]; MPL-SE, monophosphoryl lipid A in squalene emulsion (Corixa Inc. Seattle WA) [36]; and Freund's Adjuvants, CFA/IFA (Gibco, Grand Island, NY). Adjuvant dosages were per manufacturers' recommendations for usages in mice.…”

Section: Adjuvant Formulationsmentioning

confidence: 99%

Adjuvant formulations possess differing efficacy in the potentiation of antibody and cell mediated responses to a human malaria vaccine under selective immune genes knockout environment

Hui¹,

Hashimoto²

2008

International Immunopharmacology

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Infections and chronic diseases can alter the host's immunological balance or result in immunodeficiencies. We hypothesize that this may also affect the performance of vaccine adjuvants. Accordingly, the potency and adjuvanticity of eight adjuvant formulations based on Montanide ISA720, MF59, monophosphoryl lipid A (MPL), QS21 (saponin derivative), MPL-SE (stable emulsion of a MPL derivative), and MPL-AF (MPL in aqueous formulation) were studied in immune gene knockout mice, IFN-γ −/−, IL-4 −/−, and STAT6 −/−, using the P. falciparum MSP1 vaccine, P30P2MSP1-19 as a model immunogen. The adjuvants showed preferential requirements for the immune mediators to induce immune responses to MSP1-19, and the effects were formulationspecific. While emulsion-type adjuvants were highly effective in mice, their potency was more readily suppressed by immune knockouts; and additions of immunomodulators were required to restore efficacy. Formulated adjuvants had characteristics distinct from their individual components, and multi-components formulations were not necessarily superior. We conclude that perturbation of immune environments will have measurable impact on adjuvant's potency. Evaluation of adjuvants in immune knockout models may be a supplementary approach to measure and compare adjuvants' efficacy, and to further unveil their distinct biological activities.

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Structural and Immunological Characterization of the Vaccine Adjuvant QS-21

Cited by 115 publications

References 27 publications

Interleukin-6 has differential influence on the ability of adjuvant formulations to potentiate antibody reponses to a Plasmodium falciparum blood-stage vaccine

Interleukin-6 has differential influence on the ability of adjuvant formulations to potentiate antibody reponses to a Plasmodium falciparum blood-stage vaccine

Novel human polysaccharide adjuvants with dual Th1 and Th2 potentiating activity

Adjuvant formulations possess differing efficacy in the potentiation of antibody and cell mediated responses to a human malaria vaccine under selective immune genes knockout environment

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