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Amphoteric Mannan as an Immune Response Modifier. New Model Immunobiologically Active Candida albicans Mannan-Based
Ema Paulovičová1, Lucia Paulovičová1, Alžbeta Čížová2
1Institute of Chemistry, Department of Immunochemistry of Glycoconjugates, Immunology & Cell Culture Labs, Slovak Academy of Sciences, Bratislava, Slovakia.
Background:
Currently, the incidence and prevalence of serious fungal infections is increasing, especially in immunosuppressed individuals. The co-administration of antibiotic and immunosuppressive therapies has driven the emergence of new multidrug-resistant fungal pathogens. Their significant increase and their ability to form biofilms is associated with rising morbidity and mortality. Research into novel synthetically prepared immunomodulators as potential immune response modifiers and prospective participants in drug delivery systems is of interest. Microbial polysaccharides with zwitterionic charge motifs were shown to be promising candidates.
Methods:
Native and ultrasonically treated mannan from the yeast Candida albicans were chemically modified to contain both positive and negative charges in a nearly equimolar ratio mimicking the zwitterionic polysaccharides. RAW 264.7 macrophages and Balb/c mice were subjected as in vitro and in vivo models. Macrophage exposure to the set of amphoteric derivatives of mannan induced a release of Th1, Th2, Th17, and Treg cytokine signature patterns. The functionality of the exposed macrophages was assayed by cell proliferation and phagocytosis.
Results:
The Th1 and Th17 dominance was over Th2. The phagocytosis and respiratory burst, together with the viability based on cell proliferation supported the bioavailability of formulas. Mouse immunization induced humoral immune responses with high titers of the IgM isotype with the IgM/IgG shift.
Conclusion:
Our study demonstrated the immunobiological activities of amphoteric derivatives of mannan from Candida albicans. Amphoteric derivatives can be considered as bioavailable formulas with an effective immunomodulatory potency, prospectively applied as a subunit formula in the design of a mannan-based platform for drug and vaccine delivery systems.
Insights
Modified yeast mannan with zwitterionic charges shows immunomodulatory effects. These amphoteric derivatives enhance macrophage function and immune responses, offering potential for drug and vaccine delivery systems.
Area of Science:
- Immunology
- Microbiology
- Biochemistry
Background:
- Rising incidence of serious fungal infections, particularly in immunocompromised individuals.
- Emergence of multidrug-resistant fungal pathogens due to co-administered therapies.
- Need for novel immunomodulators and drug delivery systems.
Purpose of the Study:
- To chemically modify yeast mannan to create zwitterionic polysaccharides.
- To evaluate the immunobiological activities of these amphoteric mannan derivatives.
- To assess their potential in drug and vaccine delivery systems.
Main Methods:
- Chemical modification of native and ultrasonically treated Candida albicans mannan.
- In vitro studies using RAW 264.7 macrophages and in vivo studies using Balb/c mice.
- Assays for cytokine release (Th1, Th2, Th17, Treg), macrophage proliferation, and phagocytosis.
Main Results:
- Amphoteric mannan derivatives induced Th1 and Th17 cytokine dominance over Th2.
- Demonstrated enhanced macrophage phagocytosis, respiratory burst, and cell proliferation.
- Mouse immunization resulted in robust humoral immune responses with a significant IgM/IgG shift.
Conclusions:
- Amphoteric mannan derivatives exhibit significant immunobiological activities.
- These derivatives are bioavailable and possess effective immunomodulatory potency.
- Prospectively applicable as a subunit formula for mannan-based drug and vaccine delivery platforms.
