Synthesis and Immunological Studies of Linear Oligosaccharides of β-Glucan As Antigens for Antifungal Vaccine Development

Liao, Guochao; Zhou, Zhifang; Srinivas, Burgula; Liao, Jun; Yuan, Cheng; Wu, Qiuye; Guo, Zhongwu

doi:10.1021/bc500575a

Cited by 51 publications

(51 citation statements)

References 42 publications

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“…Nevertheless, it is suitable for immunologic and structure-immunogenicity relationship studies of the designed oligosaccharides and for revealing the proper antigens for vaccine development. They would also facilitate the comparison of 1a – 3a with the reported KLH conjugates of linear oligo-β-glucans 28 to gain more insights into structure-activity relationships of oligo-β-glucans. Moreover, the human serum albumin (HSA) conjugates 1b – 3b (Figure 1) of the oligo-β-glucans were prepared, which were used as coating antigens for enzyme-linked immunosorbent assays (ELISA) of carbohydrate antigen-specific antibodies.…”

Section: Resultsmentioning

confidence: 99%

6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines

et al. 2015

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With the rapid growth in fungal infections and drug-resistant fungal strains, antifungal vaccines have become an especially attractive strategy to tackle this important health problem. β-Glucans, a class of extracellular carbohydrate antigens abundantly and consistently expressed on fungal cell surfaces, are intriguing epitopes for antifungal vaccine development. β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. These glycoconjugates were proved to elicit strong IgG antibody responses in mice. It was also discovered that the number, size, and structure of branches linked to the β-glucan backbone had a significant impact on the immunologic property. Moreover, antibodies induced by the synthetic oligosaccharide-KLH conjugates were able to recognize and bind to natural β-glucans and fungal cells. Most importantly, these conjugates elicited effective protection against systemic Candida albicans infection in mice. Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates.

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Section: Resultsmentioning

confidence: 99%

6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines

et al. 2015

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“…Evidently, there is a need for an efficient and generally applicable method for β-glucan oligosaccharide synthesis. Recently, we described the efficient synthesis of linear β-glucan oligosaccharides [10] via preactivation-based glycosylation. [11] In the current paper, we report a highly convergent, efficient, and potentially generally applicable strategy for the synthesis of branched β-glucan oligosaccharides.…”

Section: Introductionmentioning

confidence: 99%

A Convergent Synthesis of 6‐O‐Branched β‐Glucan Oligosaccharides

et al. 2015

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β-Glucans are important carbohydrate antigens on the surface of fungal cells useful for antifungal vaccine development. This paper has described a highly convergent and efficient strategy for the synthesis of structurally defined branched β-glucan oligosaccharides that can be used for detailed studies of β-glucans and for the design of β-glucan-based vaccines. The strategy was highlighted by assembling the title compounds via preactivation-based glycosylation with thioglycosides as glycosyl donors. It was used to successfully prepare β-glucan oligosaccharides that had a β-1,3-linked nonaglucan backbone with β-1,6-glucotetraose, β-1,3-glucodiose and β-1,3-glucotetraose branches at the 6-O-position of the nonaglucan central sugar unit. The structure and size of the glycosyl donors and acceptors used in the syntheses did not significantly affect the glycosylation efficiency, suggesting that the strategy can be generally useful for the synthesis of more complex structures.

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“…The authors have demonstrated, using a mouse model, that the conjugate of KLH and octa-β-glucan can elicit protective immune responses against Candida albicans (78). …”

Section: Final Remarksmentioning

confidence: 99%

Linear Epitopes of Paracoccidioides brasiliensis and Other Fungal Agents of Human Systemic Mycoses As Vaccine Candidates

Travassos

Taborda

2017

Front. Immunol.

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Dimorphic fungi are agents of systemic mycoses associated with significant morbidity and frequent lethality in the Americas. Among the pathogenic species are Paracoccidioides brasiliensis and Paracoccidioides lutzii, which predominate in South America; Histoplasma capsulatum, Coccidioides posadasii, and Coccidioides immitis, and the Sporothrix spp. complex are other important pathogens. Associated with dimorphic fungi other important infections are caused by yeast such as Candida spp. and Cryptococcus spp. or mold such as Aspergillus spp., which are also fungal agents of deadly infections. Nowadays, the actual tendency of therapy is the development of a pan-fungal vaccine. This is, however, not easy because of the complexity of eukaryotic cells and the particularities of different species and isolates. Albeit there are several experimental vaccines being studied, we will focus mainly on peptide vaccines or epitopes of T-cell receptors inducing protective fungal responses. These peptides can be carried by antibody inducing β-(1,3)-glucan oligo or polysaccharides, or be mixed with them for administration. The present review discusses the efficacy of linear peptide epitopes in the context of antifungal immunization and vaccine proposition.

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Synthesis and Immunological Studies of Linear Oligosaccharides of β-Glucan As Antigens for Antifungal Vaccine Development

Cited by 51 publications

References 42 publications

6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines

6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines

A Convergent Synthesis of 6‐O‐Branched β‐Glucan Oligosaccharides

Linear Epitopes of Paracoccidioides brasiliensis and Other Fungal Agents of Human Systemic Mycoses As Vaccine Candidates

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