Synthesis and immunological studies of β-1,2-mannan-peptide conjugates as antifungal vaccines

Liao, Jun; Pan, Bo; Liao, Guochao; Zhao, Qingjie; Gao, Yun; Chai, Xin‐Sheng; Zhuo, Xiaobin; Wu, Qiuye; Jiao, Binghua; Pan, Weihua; Guo, Zhongwu

doi:10.1016/j.ejmech.2019.04.001

Cited by 19 publications

(15 citation statements)

References 48 publications

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Section: Protein Glycosylation As a Target For The Development Of Antifungal Vaccinesmentioning

confidence: 99%

“…The β-1,2-mannotriose found as part of the C. albicans cell wall phosphomannan [24] was chemically synthesized and conjugated to the N-terminal end of the adhesin Als1 [146]. When injected into mice, this conjugate stimulated the production of a specific IgG against both the trisaccharide and the peptide, in an adjuvant-free event [146]. Since these antibodies recognized the trisaccharide present in the C. albicans, C. tropicalis, C. lusitaniae, and C. glabrata wall surface, it is thought that the trisaccharide alone or conjugated to Als1 could be a candidate for the development of a vaccine against these pathogens [146].…”

Section: Protein Glycosylation As a Target For The Development Of Antifungal Vaccinesmentioning

confidence: 99%

“…When injected into mice, this conjugate stimulated the production of a specific IgG against both the trisaccharide and the peptide, in an adjuvant-free event [146]. Since these antibodies recognized the trisaccharide present in the C. albicans, C. tropicalis, C. lusitaniae, and C. glabrata wall surface, it is thought that the trisaccharide alone or conjugated to Als1 could be a candidate for the development of a vaccine against these pathogens [146]. A similar approach has also been reported, conjugating this trisaccharide to fructose-bisphosphate aldolase and to β-1,3-linked hexaglucan, in order to provide epitopes that stimulate both B and T lymphocytes, thus improving the immunological properties of the conjugate [147] [24], was conjugated to bovine serum albumin and subcutaneously inoculated in mice [148].…”

Section: Protein Glycosylation As a Target For The Development Of Antifungal Vaccinesmentioning

confidence: 99%

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Role of Protein Glycosylation in Interactions of Medically Relevant Fungi with the Host

Gómez-Gaviria

Vargas-Macías

García-Carnero

et al. 2021

JoF

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Protein glycosylation is a highly conserved post-translational modification among organisms. It plays fundamental roles in many biological processes, ranging from protein trafficking and cell adhesion to host–pathogen interactions. According to the amino acid side chain atoms to which glycans are linked, protein glycosylation can be divided into two major categories: N-glycosylation and O-glycosylation. However, there are other types of modifications such as the addition of GPI to the C-terminal end of the protein. Besides the importance of glycoproteins in biological functions, they are a major component of the fungal cell wall and plasma membrane and contribute to pathogenicity, virulence, and recognition by the host immunity. Given that this structure is absent in host mammalian cells, it stands as an attractive target for developing selective compounds for the treatment of fungal infections. This review focuses on describing the relationship between protein glycosylation and the host–immune interaction in medically relevant fungal species.

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Section: Protein Glycosylation As a Target For The Development Of Antifungal Vaccinesmentioning

confidence: 99%

Section: Protein Glycosylation As a Target For The Development Of Antifungal Vaccinesmentioning

confidence: 99%

Section: Protein Glycosylation As a Target For The Development Of Antifungal Vaccinesmentioning

confidence: 99%

See 1 more Smart Citation

Role of Protein Glycosylation in Interactions of Medically Relevant Fungi with the Host

Gómez-Gaviria

Vargas-Macías

García-Carnero

et al. 2021

JoF

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“…Yeast mannan-conjugates give promising results in allergen-specific immunotherapy by enhancing allergen bioavailability and uptake by DC [121]. In addition, these conjugates are described as efficient platforms for the development of antifungal vaccines [122].…”

Section: Biotechnological Exploitation Of Yeast To Create Vaccine mentioning

confidence: 99%

Sneaking Out for Happy Hour: Yeast-Based Approaches to Explore and Modulate Immune Response and Immune Evasion

Angrand

Quillévéré

Daskalogianni

et al. 2019

Genes

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Many pathogens (virus, bacteria, fungi, or parasites) have developed a wide variety of mechanisms to evade their host immune system. The budding yeast Saccharomyces cerevisiae has successfully been used to decipher some of these immune evasion strategies. This includes the cis-acting mechanism that limits the expression of the oncogenic Epstein–Barr virus (EBV)-encoded EBNA1 and thus of antigenic peptides derived from this essential but highly antigenic viral protein. Studies based on budding yeast have also revealed the molecular bases of epigenetic switching or recombination underlying the silencing of all except one members of extended families of genes that encode closely related and highly antigenic surface proteins. This mechanism is exploited by several parasites (that include pathogens such as Plasmodium, Trypanosoma, Candida, or Pneumocystis) to alternate their surface antigens, thereby evading the immune system. Yeast can itself be a pathogen, and pathogenic fungi such as Candida albicans, which is phylogenetically very close to S. cerevisiae, have developed stealthiness strategies that include changes in their cell wall composition, or epitope-masking, to control production or exposure of highly antigenic but essential polysaccharides in their cell wall. Finally, due to the high antigenicity of its cell wall, yeast has been opportunistically exploited to create adjuvants and vectors for vaccination.

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“…In one example, β-1,2-mannan containing peptides conjugated to protein carriers were recently explored to induce protection against infections from Candida albicans and other fungi. 75 Extensive efforts have also been put into the synthesis of sialyl Lewis X glycans as models of the natural human P-selectin ligand P-selecting glycoprotein ligand-1 (PSGL-1). 76 These might be able to inhibit the extravasation of lymphocytes into sites of chronic or acute infection, and so might alleviate symptoms of inflammation.…”

Section: Other Synthetic O-glycans For Immune Modulationsmentioning

confidence: 99%

Going Native: Synthesis of Glycoproteins and Glycopeptides via Native Linkages To Study Glycan-Specific Roles in the Immune System

2019

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Glycosylation plays a myriad of roles in the immune system: Certain glycans can interact with specific immune receptors to kickstart a pro-inflammatory response, whereas other glycans can do precisely the opposite and ameliorate the immune response. Specific glycans and glycoforms can themselves become the targets of the adaptive immune system, leading to potent antiglycan responses that can lead to the killing of altered self- or pathogenic species. This hydra-like set of roles glycans play is of particular importance in cancer immunity, where it influences the anticancer immune response, likely playing pivotal roles in tumor survival or clearance. The complexity of carbohydrate biology requires synthetic access to glycoproteins and glycopeptides that harbor homogeneous glycans allowing the probing of these systems with high precision. One particular complicating factor in this is that these synthetic structures are required to be as close to the native structures as possible, as non-native linkages can themselves elicit immune responses. In this Review, we discuss examples and current strategies for the synthesis of natively linked single glycoforms of peptides and proteins that have enabled researchers to gain new insights into glycoimmunology, with a particular focus on the application of these reagents in cancer immunology.

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Synthesis and immunological studies of β-1,2-mannan-peptide conjugates as antifungal vaccines

Cited by 19 publications

References 48 publications

Role of Protein Glycosylation in Interactions of Medically Relevant Fungi with the Host

Role of Protein Glycosylation in Interactions of Medically Relevant Fungi with the Host

Sneaking Out for Happy Hour: Yeast-Based Approaches to Explore and Modulate Immune Response and Immune Evasion

Going Native: Synthesis of Glycoproteins and Glycopeptides via Native Linkages To Study Glycan-Specific Roles in the Immune System

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