Conjugates ofanionic polyelectrolytes (PE) with betulin (PE–B) were synthesized by cross-linking the carboxyl groups oftemperature responsive poly(N-isopropylacrylamide-co-acrylic acid) (CP1) and poly(N-vinylpyrrolidoneco-acrylic acid) (CP2) copolymers, to the hydroxyl groups ofbetulin using thionyl chloride as the coupling agent. Water-insoluble CP1–B and poorly soluble CP2–B covalent conjugates were formed in a single step by mixing solutions of the selected components. Water-soluble bovine serum albumin (BSA)–betulin covalent conjugates (BSA*B) were synthesized by carbodiimide coupling. Betulin-containing polyelectrolyte conjugates (PEC–B) were prepared by complexing BSA*B conjugates with synthetic polycations – poly(N-alkyl-4-vinylpyridinium bromide). A single immunization ofmice with CP1–B and CP2–B, covalent conjugated with protein containing PEC–B and BSA*B systems without traditional adjuvants increased the specific immune response to betulin. CP2–B, as a soft and wet biocompatible delivery system, in contrast to the CP1–B conjugates, displayed an essentially higher betulin-specific immunogenic activity. The immunogenicity of BSA*B conjugates decreased rapidly with time while the PE–BSA*B complexes generated betulin-specific antibodies for 160 days.
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