From synthetic polyelectrolytes to polymer-subunit vaccines

Abstract

The results of many years of collaborative research by chemists and immunologists in the area of application of synthetic polyelectrolytes in immunology are reviewed. Linear synthetic polyelectrolytes with diverse structures (which are not structural analogs of biopolymers and, hence, not antigenic because they are unknown to the immune system), when introduced into the organism, noticeably intensify the formation, migration, and dissemination of stem cells, which are precursors of all specialized cells including functional immune cells. In addition, synthetic polyelectrolytes, when introduced in mixtures with typical antigens (proteins, natural microbial polysaccharides, and their synthetic analogs), serve as immunostimulants enhancing immune response by several times. Moreover, individual bacterial or viral antigens, not sufficiently active by themselves, induce specific immune response enhanced by orders of magnitude if chemically bound to synthetic polyelectrolytes. Such conjugates being preliminarily administrated, protect organisms from absolutely mortal doses of the corresponding bacteria or viruses. The nontoxic immunostimulant was developed: the ternary copolymer of 1,4-ethylenepiperazine, 1,4-ethylenepiperazine-N-oxide, and (N-carboxymethylene)-1,4-ethylenepiperazinium bromide (brand name "polyoxidonium"™) permitted for human administration. The conjugate of polyoxidonium with hemagglutinin and neuraminidase, protein subunits of influenza viruses, has appeared as the first non-Pasteurian vaccine, which now is successfully used in Russia (about 50 million immunized people for the last 7 years). The physicochemical mechanisms of the biological effect of these compounds and challenges of the further use of the approach developed are considered in the review.

Collagen Type II and a Thermo-Responsive Polymer of N-Isopropylacrylamide Induce Arthritis Independent of Toll-Like Receptors

“…Moreover, synthetic polymers do not generate antibodies against themselves, but may stimulate the immune system toward other antigens, thereby acting as immunostimulators. 45 PNiPAAm is a thermo-responsive polymer having a cloud point of ϳ32.5°C. Above this temperature, polymer becomes insoluble as a precipitate, and below this temperature, polymer is in solution form.…”

Dendritic cell-based vaccines in treating recurrent herpes labialis: Results of pilot clinical study

“…After washing DCs underwent maturation by culturing with Azoximer bromide (Petrovaks; 2 ng/ml) for additional 24 hours. This water-soluble cationic polymer, which hasbeen specifically designed as vaccine adjuvant 27 activates anti-inflammatory signaling pathways and enhances antigen presentation and effector cell maturation. 28,29 Cells were then washed, harvested, aliquoted at concentration of 5 £ 10 6 DCs/ml, frozen in phosphate buffer solution/10% DMSO (Sigma Aldrich, Cat N 276855) and stored in a freezer (Sanyo Ultra Low) at ¡80 C until use.…”

Polyphosphazene Vaccine Delivery Vehicles: State of Development and Perspectives

“…Further, based on existing knowledge of watersoluble polyelectrolyte complexes [30], it has been proposed that antigenpolyphosphazene complexes can adsorb on cell surfaces, resulting in clustering of membrane proteins, stimulation of intracellular ionic fluxes, and thus eventually, enhancement of the immune response [11,30]. Recent reviews on polymer genomics [31,32], uncovering the role of polymers in the induction of specific genetically controlled responses to antigens and other agents, stimulate further investigations in this direction, with a focus on cooperative interactions of polymers with plasma cell membranes and trafficking of polymers to intracellular organelles [31,32].…”

“…In summarizing the physicochemical aspects of formulation development, it is important to emphasize that other ''nonpolyphosphazene'' polyelectrolytes, such as polymethylacrylic and polyacrylic acids, are also known to display immunopotentiating activity [30]. However, it appears that their activity achieves desirable levels only if the polymer is covalently linked to the antigen [30].…”

“…However, it appears that their activity achieves desirable levels only if the polymer is covalently linked to the antigen [30]. It is clear that contrary to such systems, no covalent attachment of polyphosphazenes to the antigen is required to display an immune response of practical significance [3,9].…”