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

Abstract

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.

Vaccine Adjuvants Derived from Marine Organisms

“…Cucumarioside A 2 -2 revealed the best capacity to form tubular supramolecular complexes with cholesterol in comparison with other related triterpene glycosides of holothurians [44]. Therefore, this saponin was applied to construct nanoparticulate antigen delivery systems with adjuvant activity, which was named tubular immunostimulating complexes (TI-complexes) [45,46]. Beyond cholesterol and cucumarioside A 2 -2, TI-complexes comprise monogalactosyldiacylglycerol (MGDG) from marine algae or seagrass, which form lipid matrix for incorporation of protein antigen [47].…”

Recombinant Fusion Protein Joining E Protein Domain III of Tick-Borne Encephalitis Virus and HSP70 of Yersinia pseudotuberculosis as an Antigen for the TI-Complexes

“…As shown in Figure 4 and Table 2 , all peak maximum temperatures ( T m 1– T m 4) and therefore the thermal stability of all the HSP70/EIII domains increased in the presence of MGDG from U. lactuca , which forms a lipid matrix for antigen incorporation into the TI-complex [ 43 ]. Based on the remarkable changes in the T m 2 and transition enthalpy Δ H 2 values, the glycolipid environment had a particularly strong effect on the EIII conformation.…”

Novel Vaccine Technologies in Veterinary Medicine: A Herald to Human Medicine Vaccines

“…Chitosan, a non-toxic polymer has also been utilized in intranasally delivered Escherichia coli O157:H7 vaccine formations with similar success (244). Immunostimulating complexes (ISCOMs) are spherical cage-like experimental adjuvants composed of phospholipids, cholesterol, saponin, and protein antigens and have been particularly successful in mucosal immunizations resulting in secretory IgA and systemic immune responses (245,246). This technology has been utilized in the equine influenza vaccine Equip TM F (produced by Zoetis/Pfizer Animal Health), a subunit vaccine shown to stimulate both humoral and cell-mediated immunity (247,248).…”