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Biomed Res Int
2017 Jan 01;2017:4389525. doi: 10.1155/2017/4389525.
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Nanoparticulate Tubular Immunostimulating Complexes: Novel Formulation of Effective Adjuvants and Antigen Delivery Systems.
Sanina N
,
Chopenko N
,
Mazeika A
,
Kostetsky E
.
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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.
Figure 1. Chemical structures of glycoglycerolipids MGDG (a), DGDG (b), and SQDG (c). R1 and R2: hydrocarbon chains of fatty acid residues ((–CH2)n–CH3).
Figure 2. Electron micrograph of nanoparticles obtained after modification of ISCOMATRIX by MGDG from Laminaria japonica (magnification ×189000), taken with permission from [20].
Figure 3. Structural formulas of triterpene glycosides extracted from holothurians: (a) cucumarioside G1, (b) CDA, (c) frondoside A, and (d) holotoxin A1.
Figure 4. Electron micrographs of supramolecular complexes of cholesterol with CDA (a), HTA (b), FRA (c), and CDG (d). Bar is 100 nm, taken with permission from [44].
Figure 5. Electron micrograph of TI-complexes with weight ratio of CDA, cholesterol, and MGDG 6 : 2 : 4. Bar is 100 nm, taken with permission from [5].
Figure 6. The model of the structure for tubular immunostimulating complex (TI-complex). (1) The inner channel, (2) the layer of MGDG from marine macrophytes, (3) the layer of cholesterol-aglycone complexes, and (4) the layer of carbohydrate chains of triterpene glycoside CDA, taken with permission from [46].
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