Molecular Recognition of Candida albicans (1→2)-β-Mannan Oligosaccharides by a Protective Monoclonal Antibody Reveals the Immunodominance of Internal Saccharide Residues

Johnson, Margaret; Cartmell, Jonathan; Weisser, Nina E.; Woods, Robert J.; Bundle, David R.

doi:10.1074/jbc.m112.355578

Cited by 39 publications

(42 citation statements)

References 44 publications

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“…Whereas further characterization of the T cells activated by these compounds is required, we will first focus on optimizing vaccine conjugates. In the context of a practical C. albicans vaccine, we consider a trisaccharide B cell epitope (72) conjugated to the Fba 14 peptide (10) with attached multivalent b-glucan may provide an even more potent immunogenic compound.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Immunogenicity of a Tricomponent Mannan Tetanus Toxoid Conjugate Vaccine Targeted to Dendritic Cells via Dectin-1 by Incorporating β-Glucan

Lipiński

Fitieh

St‐Pierre

et al. 2013

The Journal of Immunology

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In a previous attempt to generate a protective vaccine against Candida albicans, a β-mannan tetanus toxoid conjugate showed poor immunogenicity in mice. To improve the specific activation toward the fungal pathogen, we aimed to target Dectin-1, a pattern-recognition receptor expressed on monocytes, macrophages, and dendritic cells. Laminarin, a β-glucan ligand of Dectin-1, was incorporated into the original β-mannan tetanus toxoid conjugate providing a tricomponent conjugate vaccine. A macrophage cell line expressing Dectin-1 was employed to show binding and activation of Dectin-1 signal transduction pathway by the β-glucan–containing vaccine. Ligand binding to Dectin-1 resulted in the following: 1) activation of Src family kinases and Syk revealed by their recruitment and phosphorylation in the vicinity of bound conjugate and 2) translocation of NF-κB to the nucleus. Treatment of immature bone marrow–derived dendritic cells (BMDCs) with tricomponent or control vaccine confirmed that the β-glucan–containing vaccine exerted its enhanced activity by virtue of dendritic cell targeting and uptake. Immature primary cells stimulated by the tricomponent vaccine, but not the β-mannan tetanus toxoid vaccine, showed activation of BMDCs. Moreover, treated BMDCs secreted increased levels of several cytokines, including TGF-β and IL-6, which are known activators of Th17 cells. Immunization of mice with the novel type of vaccine resulted in improved immune response manifested by high titers of Ab recognizing C. albicans β-mannan Ag. Vaccine containing laminarin also affected distribution of IgG subclasses, showing that vaccine targeting to Dectin-1 receptor can benefit from augmentation and immunomodulation of the immune response.

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Section: Discussionmentioning

confidence: 99%

Enhanced Immunogenicity of a Tricomponent Mannan Tetanus Toxoid Conjugate Vaccine Targeted to Dendritic Cells via Dectin-1 by Incorporating β-Glucan

Lipiński

Fitieh

St‐Pierre

et al. 2013

The Journal of Immunology

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“…To overcome this, they performed 2D 1 H-13 C STD-HSQC and 2D 1 H-13 C HSQC experiments and focused on the pyranose ring and side-chain signals. Johnson et al [61] studied molecular recognition of (1 ! 2)-β-mannan oligosaccharides by a protective monoclonal antibody.…”

Section: Sugar-protein Interactionmentioning

confidence: 99%

Recent Advances in NMR Studies of Carbohydrates

Buda¹,

Nawój²,

Młynarski³

2016

Annual Reports on NMR Spectroscopy

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“…Structural analysis revealed that internal antigenic determinants dominate recognition of β-(Man) 3 by IgG3 MAb [73]. β-mannan-specific IgM MAb could also reduce the dose of amphotericin B when used in combination in experimental candidiasis [74].…”

Section: Demonstration Of Protective Role Of Antibodies In Fungal Infmentioning

confidence: 99%

The protective role of immunoglobulins in fungal infections and inflammation

2014

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International audienceIncreased incidence of fungal infections in the immunocompromised individuals and fungi-mediated allergy and inflammatory conditions in immunocompetent individuals is a cause of concern. Consequently, there is a need for efficient therapeutic alternatives to treat fungal infections and inflammation. Several studies have demonstrated that antibodies or immunoglobulins have a role in restricting the fungal burden and their clearance. However, based on the data from monoclonal antibodies, it is now evident that the efficacy of antibodies in fungal infections is dependent on epitope specificity, abundance of protective antibodies, and their isotype. Antibodies confer protection against fungal infections by multiple mechanisms that include direct neutralization of fungi and their antigens, inhibition of growth of fungi, modification of gene expression, signaling and lipid metabolism, causing iron starvation, inhibition of polysaccharide release, and biofilm formation. Antibodies promote opsonization of fungi and their phagocytosis, complement activation, and antibody-dependent cell toxicity. Passive administration of specific protective monoclonal antibodies could also prove to be beneficial in drug resistance cases, to reduce the dosage and associated toxic symptoms of anti-fungal drugs. The longer half-life of the antibodies and flexibilities to modify their structure/forms are additional advantages. The clinical data obtained with two monoclonal antibodies should incite interests in translating pre-clinical success into the clinics. The anti-inflammatory and immunoregulatory role of antibodies in fungal inflammation could be exploited by intravenous immunoglobulin or IVIg

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Molecular Recognition of Candida albicans (1→2)-β-Mannan Oligosaccharides by a Protective Monoclonal Antibody Reveals the Immunodominance of Internal Saccharide Residues

Cited by 39 publications

References 44 publications

Enhanced Immunogenicity of a Tricomponent Mannan Tetanus Toxoid Conjugate Vaccine Targeted to Dendritic Cells via Dectin-1 by Incorporating β-Glucan

Enhanced Immunogenicity of a Tricomponent Mannan Tetanus Toxoid Conjugate Vaccine Targeted to Dendritic Cells via Dectin-1 by Incorporating β-Glucan

Recent Advances in NMR Studies of Carbohydrates

The protective role of immunoglobulins in fungal infections and inflammation

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