2 . 2025

Production of detoxified lipopolysaccharide derivatives and their applications as vaccine and adjuvant preparations

Abstract

Introduction. Due to the spread of antibiotic resistance, the search for new antibacterial vaccines and adjuvants becomes relevant. One of the promising directions is the creation of immunotropic drugs based on lipopolysaccharide (LPS) of gram-negative bacteria, which is a powerful immunostimulant and leads to the production of protective antibodies. However, the clinical use of LPS is limited by its extremely high toxicity, which can be reduced by modifying the structure of lipid A. Currently, detoxified LPS (d-LPS) and lipids A (d-LA) have been obtained, which are widely used in vaccine preparations: d-LPS – as an active substance, d-LA – as an adjuvant. In addition, the possibility of using d-LPS and d-LA as built-in adjuvants is being studied.

Structure and biological activity of LPS of gram-negative bacteria. LPS is composed of three different fragments – lipid A, core oligosaccharide and O-specific polysaccharide. The carbohydrate part of LPS provides serological specificity of different strains, lipid A activates the TLR4/MD-2 complex located on the surface of immunocompetent cells. The biological activity of lipid A is closely related to its structure: with a decrease in the number of fatty acid residues and phosphate groups, the toxicity of LPS is reduced. Thus, the classic, highly toxic lipid A of E. coli is composed of two glucosamine residues, to which 6 fatty acid residues and 2 phosphate groups are attached.

Methods for obtaining detoxified lipids A. Obtaining d-LA involves two steps – reduction of the number of fatty acid residues while retaining both phosphate groups or removal of the phosphate group while retaining the fatty acid composition. Both approaches have been successfully implemented to produce clinically applicable d-LA, OM-174 (d-LA with 3 fatty acid residues and 2 phosphate groups) and MPL (d-LA with 6 fatty acid residues and 1 phosphate group).

Methods for obtaining detoxified LPS. Obtaining d-LPS also involves removing fatty acid residues or phosphate groups by various approaches – chemical, enzymatic and genetic engineering.

Conclusion. Thus, preparations based on d-LPS and d-LA are a promising platform for the creation of new, highly immunogenic antibacterial vaccines and other immunotropic drugs. Since the production of these compounds is associated with a number of disadvantages (duration, high cost, toxicity of the reagents used), the development of new methods for obtaining d-LPS and d-LA becomes relevant.

Keywords: lipopolysaccharide; lipid A; detoxification; vaccines; adjuvants

For citation: Savin A.P., Smirnov V.V., Filatov A.V., Lvov V.L., Gudima G.O., Khaitov M.R. Production of detoxified lipopolysaccharide derivatives and their applications as vaccine and adjuvant preparations. Immunologiya. 2025; 46 (2): 243–54. DOI: https://doi.org/10.33029/1816-2134-2025-46-2-243-254 (in Russian)

Funding. The study was performed within the framework of the State assignment «Personalized Oncopreparation», R&D state registration number 124031200002-3 with the financial support of the Federal Medical and Biological Agency. Publication of the research results in the open press is allowed.

Conflict of interests. Authors declare no conflict of interests.

Authors' contributions. Concept and design of the study – Savin A.P.; literature search and analysis – Savin A.P., Filatov A.V., Lvov V.L.; figures design – Savin A.P.; writing the article – Savin A.P., Filatov A.V., Lvov V.L.; proofreading the article – Smirnov V.V., Gudima G.O., Khaitov M.R. All authors contributed to the editing of the article and approved the final version.

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