Tubular immunostimulating complex based on cucumarioside A2-2 and monogalactosyldiacylglycerol from marine macrophytes

Kostetsky, E. Ya.; Sanina, N. M.; Mazeika, Andrey; Tsybulsky, A. V.; Vorobyeva, Natalia S; Shnyrov, Valery L.

doi:10.1186/1477-3155-9-35

Cited by 17 publications

(21 citation statements)

References 22 publications

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“…The absence of the similar effect of MGDGs on immune response against HA0 s of influenza A virus and porin of Y. pseudotuberculosis [Sanina et al, 2012] suggests that the immune response is dependent not only on the components of the TI-complex and their ratio [Kostetsky et al, 2011] but the particular structure of the antigen in the content of this promising nanoparticulate adjuvant delivery system.…”

Section: Discussionmentioning

confidence: 96%

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On the Possibility of Lipid-Induced Regulation of Conformation and Immunogenicity of Influenza A Virus H1/N1 Hemagglutinin as Antigen of TI-Complexes

Vorobieva

Sanina²,

Vorontsov

et al. 2014

Microb Physiol

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The tubular immunostimulating complex (TI-complex) consisting of cucumarioside A₂-2, cholesterol and monogalactosyldiacylglycerol (MGDG) from marine macrophytes is the perspective antigen delivery system for subunit vaccines. MGDG is a lipid matrix for the protein antigen incorporated in the TI-complex. The aim of the present work was to study the influence of MGDGs from different macrophytes on conformation and immunogenicity of the secreted recombinant uncleaved hemagglutinin monomer (HA0_S) of influenza A virus H1/N1. Differential scanning calorimetry, fluorescence spectroscopy and circular dichroism showed a dependence of the conformational changes of HA0_S on the microviscosity of MGDG. The most viscous MGDG from Zostera marina induced the strongest rearrangements in protein conformation. Immunization of mice with HA0_S within TI-complexes comprising different MGDGs resulted in an approximately 2-fold increase of the levels of anti-HA0_S antibodies and granulocyte-macrophage colony-stimulating factor (GM-CSF) compared with those induced by HA0_S alone. TI-complexes based on MGDG from Z. marina stimulated the maximal production of GM-CSF. However, humoral immune response (anti-HA0_S antibodies), unlike cell-mediated immune response (GM-CSF), did not depend on the physicochemical properties of MGDGs. It is assumed that this is due to the different localization and conformational lipid sensitivity of the HA0_S regions, which are responsible for these types of immune responses.

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Section: Discussionmentioning

confidence: 96%

“…Earlier, we showed that TI-complexes provide higher adjuvant effect in comparison with ISCOMs, liposomes or Freund's complete adjuvant [Kostetsky et al, 2011].…”

mentioning

confidence: 99%

On the Possibility of Lipid-Induced Regulation of Conformation and Immunogenicity of Influenza A Virus H1/N1 Hemagglutinin as Antigen of TI-Complexes

Vorobieva

Sanina²,

Vorontsov

et al. 2014

Microb Physiol

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“…The cucumarioside A 2 -2 -cholesterol -MGalDG ratio of 6:2:4 (by weight) was found to provide the most effective formation of TI-complexes and the minimum hemolytic Toxinology DOI 10.1007/978-94-007-6650-1_3-1 # Springer Science+Business Media Dordrecht 2014 activity in vitro. The TI-complex was able to increase the immunogenicity of the protein antigens from Yersinia pseudotuberculosis by three to four times (Kostetsky et al 2011).…”

Section: Immunostimulating Complexesmentioning

confidence: 99%

Immunomodulatory Properties of Sea Cucumber Triterpene Glycosides

Aminin

2014

Marine and Freshwater Toxins

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Sea cucumbers (or holothurians) belonging to the class Holothuroidea (Echinodermata) are marine invertebrate habitually found in the benthic areas and deep seas across the world. Many holothurians are known to be toxic. Triterpene glycosides are the main poison compounds of the sea cucumbers and play a role in the defense of holothuroids as a toxin. The triterpene glycosides are composed of a carbohydrate chain and triterpene aglycone and are widely distributed in sea cucumbers. Most aglycones have 18(20)-lactones and belong to the holostane type. Carbohydrate chains of sea cucumber glycosides have from two to six monosaccharide residues including xylose, quinovose, glucose and 3-O-methylglucose and sometimes 3-O-methylxylose, 3-О-methylquinovose, 3-О-methylglucuronic acid and 6-О-acetylglucose. They may contain one, two or three sulfate groups. At the micromolar concentrations sea cucumber glycosides show hemolytic, cytotoxic, antifungal and other biological activities caused by membranotropic action. Some sea cucumber glycosides show an immunostimulatory effect at sub-toxic nanomolar concentrations. Incubation of immune cells with the glycosides induces their activation resulting in an increase of immune cell adhesion on an extracellular matrix, enhancement of cell spreading and motility, increase of macrophage lysosomal activity, ROS formation and phagocytic activity. Injection of sub-toxic doses of some glycosides induces an increase in the number of antibody-producing plaque-forming cells in mouse spleens, an increase in the number, size and acidity of lysosomes of peritoneal macrophages, an increase of phagocytic index. It was shown that glycosides moderately induce production of some cytokines, restore the level of some CD-markers of lymphocytes, increase bactericidal activity of leucocytes and induce a significant increase in mouse resistance to lethal doses of some pathogenic microorganisms and radiation. A novel nanoparticulate antigen delivery system, tubular immunostimulating complex, consisting of cholesterol, triterpene glycoside cucumarioside A 2 -2, and glycolipid monogalactosyldiacylglycerol from marine macrophytes was developed. This complex influences cytokine mechanisms of immunological regulation and its adjuvant effect varied depending on its composition. Proteomic methods have demonstrated that the mechanism of immunomodulatory action of some sea cucumber glycosides on immune cells includes regulation of the expression of certain proteins involved in formation of the immune response. These glycosides regulate the expression of proteins associated with lysosome maturation, activation and merging, phagocytosis, cytoskeletal reorganization, cell adhesion, motility and proliferation of immune cells. It was found that the most likely membrane targets of cucumarioside A 2 -2 can be purinergic receptors of P2X family. These findings suggest that this glycoside can act as an allosteric regulator which able to withdraw purine receptor inactivation by extracellular ATP and provide a recovery ...

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“…ISCOMATRIX is a flexible structure, which allows replacing their main components on structure-related compounds [ 5 ]. Therefore principally new biologically active, well-characterized components, glycoglycerolipids and saponins from marine hydrobionts, were proposed to modify and optimize ISCOMATRIX vehicles for microbial antigens [ 12 ].…”

Section: Elaboration Of Tubular Immunostimulating Complexmentioning

confidence: 99%

“…The present review summarizes literature data on properties of TI-complexes. These complexes consisting of lipid, cholesterol, and saponin [ 5 ] like their prototype, matrix of immunostimulating complex (ISCOMATRIX®) [ 3 ], are the most promising nanoparticulate adjuvant systems for the creation of effective and safe vaccines. In the present review, we discuss results published in series of our articles on elaboration, qualitative and quantitative composition, ultrastructure, and immunostimulating activity of TI-complexes.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticulate Tubular Immunostimulating Complexes: Novel Formulation of Effective Adjuvants and Antigen Delivery Systems

Sanina

Chopenko

Mazeika

et al. 2017

BioMed Research International

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New generation vaccines, based on isolated antigens, are safer than traditional ones, comprising the whole pathogen. However, major part of purified antigens has weak immunogenicity. Therefore, elaboration of new adjuvants, more effective and safe, is an urgent problem of vaccinology. Tubular immunostimulating complexes (TI-complexes) are a new type of nanoparticulate antigen delivery systems with adjuvant activity. TI-complexes consist of cholesterol and compounds isolated from marine hydrobionts: cucumarioside A2-2 (CDA) from Cucumaria japonica and monogalactosyldiacylglycerol (MGDG) from marine algae or seagrass. These components were selected due to immunomodulatory and other biological activities. Glycolipid MGDG from marine macrophytes comprises a high level of polyunsaturated fatty acids (PUFAs), which demonstrate immunomodulatory properties. CDA is a well-characterized individual compound capable of forming stable complex with cholesterol. Such complexes do not possess hemolytic activity. Ultralow doses of cucumariosides stimulate cell as well as humoral immunity. Therefore, TI-complexes comprising biologically active components turned out to be more effective than the strongest adjuvants: immunostimulating complexes (ISCOMs) and complete Freund's adjuvant. In the present review, we discuss results published in series of our articles on elaboration, qualitative and quantitative composition, ultrastructure, and immunostimulating activity of TI-complexes. The review allows immersion in the history of creating TI-complexes.

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Tubular immunostimulating complex based on cucumarioside A2-2 and monogalactosyldiacylglycerol from marine macrophytes

Cited by 17 publications

References 22 publications

On the Possibility of Lipid-Induced Regulation of Conformation and Immunogenicity of Influenza A Virus H1/N1 Hemagglutinin as Antigen of TI-Complexes

On the Possibility of Lipid-Induced Regulation of Conformation and Immunogenicity of Influenza A Virus H1/N1 Hemagglutinin as Antigen of TI-Complexes

Immunomodulatory Properties of Sea Cucumber Triterpene Glycosides

Nanoparticulate Tubular Immunostimulating Complexes: Novel Formulation of Effective Adjuvants and Antigen Delivery Systems

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