engleski

Peptidoglycan monomer - product of biotechnology with immunomodulatory properties

Peptidoglycan monomer, GlcNAc-MurNAc-L-Ala-D-isoGln-mesoDpm(eNH2)-D-Ala-D-Ala, (PGM, PLIVA, Croatia) is a natural compound originating from bacterial peptidoglycan. It was produced by a simple biotechnology procedure1. Brevibacterium divaricatum was cultured in the early exponential phase of growth in the presence of penicillin, that led to the accumulation of complex, soluble peptidoglycan (PG) - containing material in the culture fluid. Digestion of PG polymer with lysozyme and subsequent purification of hydrolysis products led to the isolation of PGM. It is a non-toxic, an apyrogenic and a water-soluble compound with completely defined chemical structure. Its immunostimulatory or adjuvant properties have clearly been demonstrated in mice model2, using ovalbumin (OVA) as an antigen. It is well known that PGM is the substrate for amidase present in the mammalian blood, and that it is very fast cleaved and excreted from the organism in the form of its metabolic products - pentapeptide and dissacharide3. It's putative metabolic products lack the adjuvant properties of the parent compound4. We hypothesised that PGM's adjuvant properties could be better exploited in adjuvant formulations that would prolong its stay in the mammals. We prepared the novel formulations of PGM and oil-based Incomplete Seppic Adjuvants, ISA 720 and ISA 206, and tested their effectiveness in mice and rabbit models. We clearly demonstrated that the novel formulations induced significantly higher levels of antigen-specific IgGs that both PGM as well as ISA adjuvants separately, and pointed out to the differences between the two experimental models used. (1Keglević et al. (1979) Biochim. Biophys. Acta 585:273 ; 2Tomašić et al. (2000) Vaccine 18:1236 ; 3Valinger et al. (1982) Biochim. Biophys. Acta 701:63 ; 4Halassy et al. (2003) Vaccine 21:971)

peptidoglycan monomer; immunomodulator; adjuvant

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