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

Eduard Y Kostetsky,Valery L Shnyrov,Alexander V Tsybulsky,Natalia S Vorobyeva,Andrey N Mazeika,Nina M Sanina

doi:10.1186/1477-3155-9-35

Eduard Y Kostetsky, Valery L Shnyrov + Show 4 more

Open Access

https://doi.org/10.1186/1477-3155-9-35

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Abstract

BackgroundThere is an urgent need to develop safe and effective adjuvants for the new generation of subunit vaccines. We developed the tubular immunostimulating complex (TI-complex) as a new nanoparticulate antigen delivery system. The morphology and composition of TI-complexes principally differ from the known vesicular immunostimulating complexes (ISCOMs). However, methodology for the preparation of TI-complexes has suffered a number of shortcomings. The aim of the present work was to obtain an antigen carrier consisting of triterpene glycosides from Cucumaria japonica, cholesterol, and monogalactosyldiacylglycerol from marine macrophytes with reproducible properties and high adjuvant activity.ResultsThe cucumarioside A2-2 - cholesterol - MGalDG ratio of 6:2:4 (by weight) was found to provide the most effective formation of TI-complexes and the minimum hemolytic activity in vitro. Tubules of TI-complexes have an outer diameter of about 16 nm, an inner diameter of 6 nm, and a length of 500 nm. A significant dilution by the buffer gradually destroyed the tubular nanoparticles. The TI-complex was able to increase the immunogenicity of the protein antigens from Yersinia pseudotuberculosis by three to four times.ConclusionsWe propose an optimized methodology for the preparation of homogeneous TI-complexes containing only tubular particles, which would achieve reproducible immunization results. We suggest that the elaborated TI-complexes apply as a universal delivery system for different subunit antigens within anti-infectious vaccines and enhance their economic efficacy and safety.

Highlights

There is an urgent need to develop safe and effective adjuvants for the new generation of subunit vaccines
We proposed principally new biologically active components, glycoglycerolipids and triterpene glycosides isolated from marine macrophytes and invertebrates, respectively, to modify and optimize immunostimulating complexes (ISCOMs) vehicles for microbial antigens
We developed a prototype of TIcomplex consisting of the sum of monosulfated triterpene glycosides from Cucumaria japonica, cholesterol, and MGalDG from marine macrophytes with a component weight ratio of 3:2:6, respectively

Summary

Introduction

There is an urgent need to develop safe and effective adjuvants for the new generation of subunit vaccines. The side effects of ISCOMs are their toxicity, caused by the presence of the hemolytic saponins of Q. saponaria [2,6], a consistently insufficient adjuvant activity, and the absence of a satisfactory method of tubular superstructure of the complexes (TI-complexes) instead of the vesicular one of classical ISCOMs [12]. Based on these results, we developed a prototype of TIcomplex consisting of the sum of monosulfated triterpene glycosides from Cucumaria japonica, cholesterol, and MGalDG from marine macrophytes with a component weight ratio of 3:2:6, respectively. Biological tests of the TI-complex prototype revealed that it had adjuvant activity [14,15,16]

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