Three double-blind, randomized trials evaluating the safety and tolerance of different formulations of the saponin adjuvant QS-21

Waite, Douglas C.; Jacobson, Eric; Ennis, Francis A.; Edelman, Robert; White, Benjamin Thomas; Kammer, Robert B.; Anderson, Charles M.; Kensil, Charlotte R.

doi:10.1016/s0264-410x(01)00142-6

Cited by 118 publications

(57 citation statements)

References 22 publications

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“…QS-21 is a Th1 adjuvant that enhances both humoral and cell-mediated immune responses. However, it has serious drawbacks such as high toxicity, a high hemolytic effect, instability in the aqueous phase, and commercial unavailability [33]. This has led to additional research for alternative adjuvants.…”

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confidence: 99%

Platycodin D Improves the Immunogenicity of Newcastle Disease Virus‐Based Recombinant Avian Influenza Vaccine in Mice

Xie

Sun

2010

Chemistry & Biodiversity

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The development of an effective influenza vaccine is urgently important for controlling outbreaks of the highly pathogenic avian influenza virus (HPAIV) and reducing the impact of pandemics. The use of an adjuvant in such a vaccine can significantly contribute to improve the immunogenicity. To explore a novel and safe adjuvant for improving the potency of influenza vaccines, platycodin D (1), a saponin from the root of Platycodon grandiflorum, was evaluated for the adjuvant potentials on the specific cellular and humoral immune responses to Newcastle disease virus-based recombinant avian influenza vaccine (rL-H5) in mice. Compound 1 significantly promoted the concanavalin A (Con A)-, the lipopolysaccharide (LPS)-, and the antigen-induced splenocyte proliferation and enhanced the serum antigen-specific IgG, IgG1, IgG2a, and IgG2b antibody titers (P<0.05, P<0.01, or P<0.001) in mice immunized with rL-H5. The mRNA expressions of Th1/Th2 cytokines (IFN-gamma and IL-10) and transcription factors (T-bet and GATA-3) in splenocytes were also markedly up-regulated by 1, compared with the control group immunized with rL-H5 alone (P<0.01 or P<0.001). In addition, 1 remarkably increased the killing activities of natural killer (NK) cells from splenocytes in the immunized mice (P<0.05), which may have important implications for the vaccination against the avian influenza virus. We concluded that 1 could improve the immunogenicity of the rL-H5 vaccine by enhancing both humoral and cellular immune responses in mice, and that 1 is a promising adjuvant for influenza vaccines.

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confidence: 99%

Platycodin D Improves the Immunogenicity of Newcastle Disease Virus‐Based Recombinant Avian Influenza Vaccine in Mice

Xie

Sun

2010

Chemistry & Biodiversity

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“…Several potential adjuvants are in various stages of research and development including monophosphoryl lipid A (20), CpG oligonucleotides (25), saponins (26), and lipid vesicles (10). One of the most significant limitations to these preparations, besides their often severe side effects (24), are their structural constraints, where small modifications of the base structure result in either increased toxicity or decreased efficacy (15).…”

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confidence: 99%

Adjuvant Activity of Emulsan, a Secreted Lipopolysaccharide from Acinetobacter calcoaceticus

Panilaitis

Johri

Blank

et al. 2002

Clin Vaccine Immunol

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Several promising adjuvant candidates have been studied over the past 75 years; however, only alum is currently approved for human use. The complex acylated polysaccharide emulsan, secreted from Acinetobacter calcoaceticus, represents a new candidate. Unique features of this family of polymers are their amenability to structural tailoring and their emulsification behavior. We demonstrate that emulsan activates macrophages in a dose-dependent manner. This activation is dependent on the presence of the fatty acid side chains that decorate the polysaccharide backbone, and, furthermore, the level of activation can be affected by changes in the chemical characteristics of emulsan structural variants. One emulsan variant was examined in a classical hapten carrier immunization protocol and demonstrated significant adjuvant activity as determined by haptenspecific antibody titers. This immune response was characterized by a high immunoglobulin G2a titer, consistent with a Th1 response. The significant immunopotentiation demonstrated by this complex polymer establishes emulsan as an exciting new candidate adjuvant. Furthermore, by manipulating the chemical structure of this compound, we can explore the physical basis of pattern recognition receptors and macrophage activation.Taking its name from the Latin word adjuvare, which means to help, an adjuvant is any compound that increases the strength and/or duration of an immune response to a foreign antigen over that caused by the antigen alone (19). The important characteristics of an adjuvant are its ability to enhance the immune response to the target antigen, long-term safety in widespread application, and flexibility in its use for different antigen and disease systems.Since its adjuvant activity was first described over 75 years ago (6), alum remains the only adjuvant approved for use in humans (5). Several potential adjuvants are in various stages of research and development including monophosphoryl lipid A (20), CpG oligonucleotides (25), saponins (26), and lipid vesicles (10). One of the most significant limitations to these preparations, besides their often severe side effects (24), are their structural constraints, where small modifications of the base structure result in either increased toxicity or decreased efficacy (15).Emulsan is a complex extracellular acylated polysaccharide produced by the gram-negative bacterium Acinetobacter calcoaceticus, which is ubiquitous in nature and which is considered to be part of the normal human commensal load (3, 4). Emulsan has been extensively researched for its industrial applications as an emulsifier (7-9, 13, 21, 27, 28). This molecule is composed of an unbranched polysaccharide backbone with O-acyl and N-acyl bound fatty acid side chains. The polysaccharide backbone consists of three aminosugars, D-galactosamine, D-galactosaminouronic acid, and a dideoxydiaminohexose in the ratio 1:1:1 (2, 9). The fatty acid side chains range in length from 10 to 22 carbons and can represent from 5 to 23% (wt/wt) of the polymer. The emu...

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“…Compelling data from laboratory studies, epidemiological investigations, and human clinical trials all have demonstrated that saponins have significant potential in cancer chemoprevention and chemotherapy. [3][4][5][6][7] The dried rhizome of Ardisia gigantifolia STAPF. (Myrsinaceae) is mainly used as Chinese folk medicine in south of China for the treatment of rheumatism, muscle and bone pain, and traumatic injury.…”

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Antitumor Activity of Triterpenoid Saponin-Rich Adisia gigantifolia Extract on Human Breast Adenocarcinoma Cells in Vitro and in Vivo

Bai

Dong

et al. 2014

Biological & Pharmaceutical Bulletin

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The aim of this study was to explore whether the ethanolic extract of Ardisia gigantifolia rhizomes (AGB-5), a traditional herbal medicine from China, could affect the proliferation of human breast adenocarcinoma (MCF-7) cells in vitro and to explore the antitumor effects of AGB-5 in BALB/c mice engrafted with MCF-7 cells. The results showed that AGB-5 markedly inhibited the proliferation of MCF-7 cells with an IC 50 value of 11.89 1.12 µg/mL, increased the S phase and decreased the G2/M phase without influence on G1 phase. MCF-7 cells treated with AGB-5 presented a dose-dependent increase of apoptosis compared with the control group. AGB-5 also significantly increased the activity of caspase-3 and -9 in a dose-dependent manner in MCF-7 cells. Furthermore, in an in vivo model, AGB-5 reduced tumor volume, brought back the red blood cell (RBC) and white blood cell (WBC) count near to normal value, enhanced superoxide dismutase and catalase level of MCF-7 bearing mice. This is the first study to verify the antitumor activity of A. gigantifolia in vivo. The results suggest that AGB-5 may have potential beneficial effects against human breast adenocarcinoma.Key words anticancer; cell cycle arrest; apoptosis; catalase; superoxide dismutase (SOD)Many of the currently used cancer chemotherapy drugs are either directly derived or chemically synthesized active principles of natural products.1) Natural products have proven to be rich sources of leads for compounds with anticancer properties. According to a recent report, 63% of anticancer agents approved between 1981 and 2008 were natural products, natural-product-derived, or natural product-inspired.2) The discovery of novel anticancer agents has progressed considerably in recent years. Compelling data from laboratory studies, epidemiological investigations, and human clinical trials all have demonstrated that saponins have significant potential in cancer chemoprevention and chemotherapy. 3-7)The dried rhizome of Ardisia gigantifolia STAPF. (Myrsinaceae) is mainly used as Chinese folk medicine in south of China for the treatment of rheumatism, muscle and bone pain, and traumatic injury. A kind of evergreen dwarf shrub, it is distributed in the provinces of Guangxi, Jiangxi, and Fujian in China.8) Previous chemical studies showed that triterpenoid saponins were the main components from this genus. Many triterpenoid saponins have been isolated from the rhizome of A. gigantifolia. 9) We recently isolated a series of new oleanane-type triterpenoid saponins from the rhizome of A. gigantifolia with the former compounds exhibiting cytotoxicity against human cancer cell lines. 10-12)The current study is one of the first efforts to verify the antitumor activity of A. gigantifolia using an animal model. Ethanol extract of A. gigantifolia rhizome (AGB-5) was selected for this study because it is rich in active saponins. The present study was designed to explore the mechanisms of the antitumor effects of AGB-5 on the MCF-7 cell line, as well as the antitumor effects of AGB-5 in BALB/...

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Three double-blind, randomized trials evaluating the safety and tolerance of different formulations of the saponin adjuvant QS-21

Cited by 118 publications

References 22 publications

Platycodin D Improves the Immunogenicity of Newcastle Disease Virus‐Based Recombinant Avian Influenza Vaccine in Mice

Platycodin D Improves the Immunogenicity of Newcastle Disease Virus‐Based Recombinant Avian Influenza Vaccine in Mice

Adjuvant Activity of Emulsan, a Secreted Lipopolysaccharide from Acinetobacter calcoaceticus

Antitumor Activity of Triterpenoid Saponin-Rich <i>Adisia gigantifolia</i> Extract on Human Breast Adenocarcinoma Cells <i>in Vitro</i> and <i>in Vivo</i>

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