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Adjuvant activity of peptidoglycan monomer and its metabolic products
Beata Halassy1, Marina Krstanović, Ruza Frkanec
1Research and Development Department, Institute of Immunology Inc, Rockefellerova 10, HR-10 000, Zagreb, Croatia. bhalassy@imz.hr
Abstract:
Peptidoglycan monomer (PGM) is a natural compound of bacterial origin. It is a non-toxic, non-pyrogenic, water-soluble immunostimulator potentiating humoral immune response to ovalbumin (OVA) in mice. It is fast degraded and its metabolic products-the pentapeptide (PP) and the disaccharide (DS)-are excreted from the mammalian organism upon parenteral administration. The present study investigates: (a). whether PGM could influence the long-living memory generation; (b). whether metabolic products retain adjuvant properties of the parent compound and contribute to its adjuvanticity. We report now that mice immunised twice with OVA+PGM had significantly higher anti-OVA IgG levels upon challenge with antigen alone 6 months later in comparison to control group immunised with OVA only. PP and DS were prepared enzymatically in vitro as apyrogenic and chemically pure compounds. When mice were immunised with OVA plus PP and DS, respectively, the level of anti-OVA IgGs in sera was not higher than in mice immunised with OVA alone, while PGM raised the level of specific antibodies. Results implicate that the adjuvant active molecule, capable of enhancing long-living memory generation, is PGM itself, and none of its metabolic products.
Insights
Peptidoglycan monomer (PGM) enhances long-term immune memory against ovalbumin (OVA) in mice. Its metabolic products, pentapeptide (PP) and disaccharide (DS), do not possess the same adjuvant properties as PGM.
Area of Science:
- Immunology
- Microbiology
- Biochemistry
Background:
- Peptidoglycan monomer (PGM) is a bacterial compound with immunostimulatory properties.
- PGM is non-toxic, water-soluble, and potentiates humoral immune responses.
- PGM is rapidly degraded into pentapeptide (PP) and disaccharide (DS), which are excreted.
Purpose of the Study:
- To investigate if PGM influences the generation of long-living immunological memory.
- To determine if PGM's metabolic products (PP and DS) retain adjuvant properties.
- To identify the specific molecule responsible for PGM's adjuvanticity.
Main Methods:
- Mice were immunized twice with ovalbumin (OVA) combined with PGM, PP, or DS.
- Humoral immune response was assessed by measuring anti-OVA IgG levels.
- Long-term memory was evaluated by challenging mice with OVA alone 6 months post-immunization.
Main Results:
- Mice immunized with OVA+PGM showed significantly higher anti-OVA IgG levels upon challenge compared to controls.
- Immunization with OVA+PP or OVA+DS did not result in elevated anti-OVA IgG levels.
- PGM administration led to a notable increase in specific antibody levels.
Conclusions:
- Peptidoglycan monomer (PGM) itself is the active adjuvant molecule responsible for enhancing long-living memory generation.
- The metabolic products, pentapeptide (PP) and disaccharide (DS), do not contribute to PGM's adjuvanticity.
- PGM's ability to potentiate immune memory is intrinsic to the parent compound.
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