QS-21
(Synonyms: 皂苷QA21V1,Stimulon) 目录号 : GC63377
QS-21是一种免疫刺激性皂苷，可用作有效的疫苗佐剂。
Cas No.:141256-04-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >90.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
QS-21 is an immune-stimulatory saponin that can be used as an effective vaccine adjuvant[1]. QS-21 enhances vaccine immune responses by activating dendritic cells and helper T cells, promoting antibody production and cell-mediated immune responses[2]. QS-21 is an activator of the NLRP3 inflammasome and leads to subsequent release of caspase-1-dependent pro-inflammatory cytokines IL-1β and IL-18[3].
In vitro, QS-21 (2.5, 5, 25 μM) treatment of HUVEC and PBMC cells for 24 hours significantly reduced cell viability, with this cytotoxic effect being more pronounced in HUVEC cells[4]. QS-21 (0-50 μM) treatment of two human gastric cancer cell lines (SNU 1 and KATO III) and a normal human cell line (GES-1) for 24 hours resulted in dose-dependent toxicity in KATO III and SNU 1 cells, with IC50 values of 67μM and 13.6μM, respectively, but showed almost no cytotoxicity to GES-1 cells[5].
In vivo, immunization of mice with Aβ42 formulated with QS-21 adjuvant produced the highest antibody titers, followed by CFA/IFA > alum > TMG[6].
References:
[1] Marty-Roix R, Vladimer G I, Pouliot K, et al. Identification of QS-21 as an inflammasome-activating molecular component of saponin adjuvants[J]. Journal of Biological Chemistry, 2016, 291(3): 1123-1136.
[2] Welsby I, Detienne S, N’Kuli F, et al. Lysosome-dependent activation of human dendritic cells by the vaccine adjuvant QS-21[J]. Frontiers in immunology, 2017, 7: 663.
[3] Lacaille-Dubois M A. Updated insights into the mechanism of action and clinical profile of the immunoadjuvant QS-21: A review[J]. Phytomedicine, 2019, 60: 152905.
[4] Campos-Estrada C, Riquelme B, Vergara M, et al. In vitro Notch-mediated adjuvant immunogenic potency is induced by combining QS-21 and MPL in a co-culture model of PBMC and HUVEC cells[J]. Toxicology in Vitro, 2020, 68: 104947.
[5] Guzmán L, Villalón K, Marchant M J, et al. In vitro evaluation and molecular docking of QS-21 and quillaic acid from Quillaja saponaria Molina as gastric cancer agents[J]. Scientific Reports, 2020, 10(1): 10534.
Cribbs D H, Ghochikyan A, Vasilevko V, et al. Adjuvant‐dependent modulation of Th1 and Th2 responses to immunization with β‐amyloid[J]. International immunology, 2003, 15(4): 505-514.
QS-21是一种免疫刺激性皂苷，可用作有效的疫苗佐剂[1]。QS-21的作用是增强疫苗的免疫反应，它通过激活树突状细胞和辅助T细胞，促进抗体生成和细胞介导的免疫反应[2]。QS-21是NLRP3炎症小体的激活剂，并导致caspase-1依赖性促炎细胞因子I1-1β / I1-18的后续释放[3]。
在体外，QS-21（2.5, 5, 25μM）处理HUVEC、PBMC细胞24 h，显著降低了细胞存活率，这种细胞毒性作用在HUVEC细胞中更为明显[4]。QS-21（0-50μM）处理两种人胃癌细胞系（SNU 1和KATO III）和人正常细胞系（GES-1）24h，以剂量依赖性方式对KATO III和SNU 1细胞产生毒性作用，IC50 值分别为67µM和13.6µM，但是对GES-1细胞几乎没有细胞毒性[5]。
在体内，使用QS-21佐剂配制的Aβ42对小鼠进行免疫加强，产生的抗体效价最高，随后是CFA/IFA >明矾> TMG[6]。
| Cas No. | 141256-04-4 | SDF | |
| 别名 | 皂苷QA21V1,Stimulon | ||
| 分子式 | C92H148O46 | 分子量 | 1990.13 |
| 溶解度 | DMSO : 100 mg/mL (50.25 mM; Need ultrasonic); H2O : 50 mg/mL (25.12 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 0.5025 mL | 2.5124 mL | 5.0248 mL |
| 5 mM | 0.1005 mL | 0.5025 mL | 1.005 mL |
| 10 mM | 0.0502 mL | 0.2512 mL | 0.5025 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Updated insights into the mechanism of action and clinical profile of the immunoadjuvant QS-21: A review
Phytomedicine 2019 Jul;60:152905.PMID:31182297DOI:10.1016/j.phymed.2019.152905.
Background: Vaccine adjuvants are compounds that significantly enhance/prolong the immune response to a co-administered antigen. The limitations of the use of aluminium salts that are unable to elicite cell responses against intracellular pathogens such as those causing malaria, tuberculosis, or AIDS, have driven the development of new alternative adjuvants such as QS-21, a triterpene saponin purified from Quillaja saponaria. Purpose: The aim of this review is to attempt to clarify the mechanism of action of QS-21 through either receptors or signaling pathways in vitro and in vivo with special emphasis on the co-administration with other immunostimulants in new adjuvant formulations, called adjuvant systems (AS). Furthermore, the most relevant clinical applications will be presented. Methods: A literature search covering the period 2014-2018 was performed using electronic databases from Sci finder, Science direct, Medline/Pubmed, Scopus, Google scholar. Results: Insights into the mechanism of action of QS-21 can be summarized as follows: 1) in vivo stimulation of Th2 humoral and Th1 cell-mediated immune responses through action on antigen presenting cells (APCs) and T cells, leading to release of Th1 cytokines participating in the elimination of intracellular pathogens. 2) activation of the NLRP3 inflammasome in mouse APCs with subsequent release of caspase-1 dependent cytokines, Il-1β and Il-18, important for Th1 responses. 3) synthesis of nearly 50 QS-21 analogs, allowing structure/activity relationships and mechanistic studies. 4) unique synergy mechanism between monophosphoryl lipid A (MPL A) and QS-21, formulated in a liposome (AS01) in the early IFN-γ response, promoting vaccine immunogenicity. The second part of the review is related to phase I-III clinical trials of QS-21, mostly formulated in ASs, to evaluate efficacy, immunogenicity and safety of adjuvanted prophylactic vaccines against infectious diseases, e.g. malaria, herpes zoster, tuberculosis, AIDS and therapeutic vaccines against cancer and Alzheimer's disease. Conclusion: The most advanced phase III clinical applications led to the development of two vaccines containing QS-21 as part of the AS, the Herpes Zoster vaccine (HZ/su) (Shingrix™) which received a license in 2017 from the FDA and a marketing authorization in the EU in 2018 and the RTS,S/AS01 vaccine (Mosquirix™) against malaria, which was approved by the EMA in 2015 for further implementation in Sub-Saharan countries for routine use.
Synthetic Investigation toward QS-21 Analogues
Org Lett 2020 Nov 6;22(21):8613-8617.PMID:33074676DOI:10.1021/acs.orglett.0c03185.
With glycosyl o-alkynylbenzotes as donors, a highly efficient protocol to construct the challenging glycosidic linkages at C3-OH of C23-oxo oleanane triterpenoids is disclosed, on the basis of which different strategies for the highly efficient synthesis of QS-21 analogues with the west-wing trisaccharide of QS-21 have been established.
Adjuvant system AS01: helping to overcome the challenges of modern vaccines
Expert Rev Vaccines 2017 Jan;16(1):55-63.PMID:27448771DOI:10.1080/14760584.2016.1213632.
Adjuvants are used to improve vaccine immunogenicity and efficacy by enhancing antigen presentation to antigen-specific immune cells with the aim to confer long-term protection against targeted pathogens. Adjuvants have been used in vaccines for more than 90 years. Combinations of immunostimulatory molecules, such as in the Adjuvant System AS01, have opened the way to the development of new or improved vaccines. Areas covered: AS01 is a liposome-based vaccine adjuvant system containing two immunostimulants: 3-O-desacyl-4'-monophosphoryl lipid A (MPL) and the saponin QS-21. Here we describe studies investigating the mode of action of AS01, and consider the role of AS01 in enhancing specific immune responses to the antigen for selected candidate vaccines targeting malaria and herpes zoster. The effects of AS01 are rapid and transient, being localized to the injected muscle and draining lymph node. AS01 is efficient at promoting CD4+ T cell-mediated immune responses and is an appropriate candidate adjuvant for inclusion in vaccines targeting viruses or intracellular pathogens. Expert commentary: AS01 activity to enhance adaptive responses depends on synergistic activities of QS-21 and MPL. AS01 adjuvantation shows good prospects for use in new vaccines targeted to populations with challenging immune statuses and against diseases caused by complex pathogens.
Correlates of adjuvanticity: A review on adjuvants in licensed vaccines
Semin Immunol 2018 Oct;39:14-21.PMID:29801750DOI:10.1016/j.smim.2018.05.001.
After decades of slow progress, the last years have seen a rapid acceleration of the development of adjuvanted vaccines which have lately been approved for human use. These adjuvants consist of different components, e.g. aluminium salts, emulsions such as MF59 and AS03, Toll-like receptor (TLR) agonists (CpG ormonophosphoryl lipid A (MPL) adsorbed on aluminium salts as in AS04) or combination of immunopotentiators (QS-21 and MPL in AS01). Despite their distinctive features, most of these adjuvants share some key characteristics. For example, they induce early activation (although at different levels) of innate immunity which then translates into higher antibody and cellular responses to the vaccine antigens. In addition, most of these adjuvants (e.g. MF59, AS03, AS04) clearly induce a wider breadth of adaptive responses able to confer protection against, for example, heterovariants of the influenza viruses (MF59, AS03) or against human papillomavirus strains not contained in the vaccine (AS04). Finally, the use of some of these adjuvants has contributed to significantly enhance the immune response and the efficacy and effectiveness of vaccines in the elderly who experience a waning of the immune responsiveness to infection and vaccination, as shown for MF59- or AS03-adjuvanted influenza vaccines and AS01-adjuvanted herpes zoster vaccine. These results, together with the track record of acceptable safety profiles of the adjuvanted vaccines, pave the way for the development of novel vaccines at the extremes of age and against infections with a high toll of morbidity and mortality. Here, we review the mechanisms associated with the performance of those adjuvanted vaccines in animal models and in humans through recent advances in systems vaccinology and biomarker discovery. We also provide some perspectives on remaining knowledge gaps but also on opportunities that could accelerate the development of new vaccines.
QS-21 Adjuvant: Laboratory-Scale Purification Method and Formulation Into Liposomes
Methods Mol Biol 2017;1494:73-86.PMID:27718186DOI:10.1007/978-1-4939-6445-1_5.
QS-21, a saponin extracted from the tree Quillaja saponaria Molina, is a vaccine adjuvant which has been shown to elicit robust antibody and cell-mediated immune responses in a variety of preclinical and clinical studies [1]. Its purification from the natural source is a lengthy and difficult process. The commercially available saponin mixture Quil-A® is a fraction of the bark extract containing a variety of saponins, including QS-21. In order to facilitate access to QS-21 at laboratory-scale amounts, we propose here a method of purification of QS-21 starting from Quil-A®. In addition, we describe a protocol to appropriately formulate QS-21 into cholesterol-containing, neutral liposomes which are known to decrease QS-21's hemolytic activity while retaining the adjuvant effect. Methods for the physicochemical characterization of purified QS-21 and of the QS-21/liposome formulations are also described.