Amphoteric Mannan as an Immune Response Modifier. New Model Immunobiologically Active Candida albicans Mannan-Based Formula

ABSTRACT

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.

Graphical abstract

KEYWORDS:

• Amphoteric mannan
• antibodies
• Candida albicans
• cytokines
• immunization
• RAW cells

Disclosure statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

CRediT authorship contribution statement

EP: Conceptualization, Methodology, Formal analysis, Investigation, Writing – Original Draft, Visualization.

LP: Formal analysis, Investigation, Writing – Review & Editing, Visualization.

AČ: Methodology, Investigation, Writing – Original Draft, Visualization, Funding acquisition.

JM: Investigation, Writing – Review & Editing.

PF: Methodology, Investigation, Writing – Review & Editing, Funding acquisition, Animals handling and management.

SB: Conceptualization, Writing – Original Draft.

RV: Methodology.

Supplementary data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/08820139.2023.2186245

Additional information

Funding

This work was supported by the Grant Agency of the Slovak Academy of Sciences VEGA [grant number 2/0076/21], the Slovak Research and Development Agency [grant number APVV-15-0161], Operational Program Integrated Infrastructure for the project Study of structural changes of complex glycoconjugates in the process of inherited metabolic and civilization diseases, ITMS: 313021Y920, co-financed by the European Regional Development Fund and is based upon work from COST Action CA16231 ENOVA (European Network of Vaccine Adjuvants). This publication is the result of the project implementation CEMBAM – Centre for Medical Bio-Additive Manufacturing and Research, ITMS2014+: 313011V358 supported by the Operational Programme Integrated Infrastructure funded by the European Regional Development Fund.