Deciphering the structure–immunogenicity relationship of anti-Candidaglycoconjugate vaccines

Abstract

Elucidation of the molecular immunity of glycoconjugate vaccines has focused on the carbohydrate moiety, herein the effect of the corresponding conjugation sites is studied.

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

“…This can remarkably reduce the number of synthetic and purification steps as compared to the reported methods. [8b, 15] Three complex β-glucan oligosaccharides with β-1,3- and β-1,6-oligoglucose branches were efficiently assembled by the new strategy. It was further observed that the structure and the size of glycosyl donors and acceptors employed for preactivation-based glycosylation had little influence on the reaction efficiency, suggesting that this synthetic strategy may be broadly useful for constructing more complex oligosaccharides with good yields.…”

“…[6] It has also been shown that β-glucans could induce strong immune responses [4] and that a vaccine composed of natural β-glucans could engender effective protection against Candida albican and Aspergillus fumigatus infections in mouse. [7] In addition, the CRM 197 protein conjugates of β-glucan oligosaccharides have been revealed to elicit immune responses comparable to that induced by the conjugates of natural β-glucans, [8] demonstrating that the oligosaccharide analogs of natural β-glucans are useful for antifungal vaccine development.…”

“…To study these issues and to develop β-glucan-based vaccines, it is essential to have access to homogeneous and structurally defined β-glucan oligosaccharides. Although several linear β-glucan oligosaccharides and an oligosaccharide with monosaccharide branches were previously prepared by hydrolysis of natural β-glucans or by chemical synthesis, [8] current strategies have drawbacks that have limited their synthetic efficiency and applicability, especially in the synthesis of complex structures. Evidently, there is a need for an efficient and generally applicable method for β-glucan oligosaccharide synthesis.…”

The evaluation of β-(1 → 3)-nonaglucoside as an anti-Candida albicansimmune response inducer

“…Extensive investigations of this notion in the past decade have stimulated considerable activity in the synthesis of β-(1 → 3)-glucan-related oligosaccharides and demonstrated that conjugates of either natural β-(1 → 3)-glucans from different sources (Torosantucci et al, 2005;Bromuro et al, 2010) or synthetic β-(1 → 3)linked oligoglucosides (Bromuro et al, 2010;Adamo et al, 2011;Hu et al, 2013;Adamo et al, 2014;Liao et al, 2015) with carrier proteins are immunogenic (Torosantucci et al, 2005;Bromuro et al, 2010;Adamo et al, 2011;Hu et al, 2013;Adamo et al, 2014;Liao et al, 2015) and protective (Torosantucci et al, 2005;Bromuro et al, 2010;Liao et al, 2015) in mice against infections induced by C. albicans and Aspergillus fumigatus. Extensive investigations of this notion in the past decade have stimulated considerable activity in the synthesis of β-(1 → 3)-glucan-related oligosaccharides and demonstrated that conjugates of either natural β-(1 → 3)-glucans from different sources (Torosantucci et al, 2005;Bromuro et al, 2010) or synthetic β-(1 → 3)linked oligoglucosides (Bromuro et al, 2010;Adamo et al, 2011;Hu et al, 2013;Adamo et al, 2014;Liao et al, 2015) with carrier proteins are immunogenic (Torosantucci et al, 2005;Bromuro et al, 2010;Adamo et al, 2011;Hu et al, 2013;Adamo et al, 2014;Liao et al, 2015) and protective (Torosantucci et al, 2005;Bromuro et al, 2010;Liao et al, 2015) in mice against infections induced by C. albicans and A...…”

“…The overall presence of β-(1 → 3)-glucan, pan-fungal antigen in the cell wall of all human pathogenic fungi makes this glycopolymer a rational target for the development of vaccines capable of protecting against multiple fungal pathogens. Extensive investigations of this notion in the past decade have stimulated considerable activity in the synthesis of β-(1 → 3)-glucan-related oligosaccharides and demonstrated that conjugates of either natural β-(1 → 3)-glucans from different sources (Torosantucci et al, 2005;Bromuro et al, 2010) or synthetic β-(1 → 3)linked oligoglucosides (Bromuro et al, 2010;Adamo et al, 2011;Hu et al, 2013;Adamo et al, 2014;Liao et al, 2015) with carrier proteins are immunogenic (Torosantucci et al, 2005;Bromuro et al, 2010;Adamo et al, 2011;Hu et al, 2013;Adamo et al, 2014;Liao et al, 2015) and protective (Torosantucci et al, 2005;Bromuro et al, 2010;Liao et al, 2015) in mice against infections induced by C. albicans and Aspergillus fumigatus. Moreover, tested forms of Saccharomyces cerevisiae glucan, i.e.…”