Beta-glucan-CRM197 conjugates as candidates antifungal vaccines

A laminarin-diphtheria toxoid (CRM197) conjugate vaccine conferred protection against fungal infections in mice. We have now generated novel β-glucan-CRM197 vaccines, with either natural (Curd-CRM197) or synthetic linear (15mer-CRM197), or β-(1,6)-branched (17mer-CRM197) β-(1,3)-oligosaccharides, formulated with the human-acceptable adjuvant MF59. Curd-CRM197 and 15mer-CRM197 conjugates, which induced high titers of anti-β-(1,3)-glucan IgG, but no antibodies against β-(1,6)-glucan, conferred protection to mice lethally challenged with C. albicans. In contrast, the 17mer-CRM197 conjugate, which induced anti-β-(1,6)-glucan antibodies in addition to the anti-β-(1,3)-glucan IgG, was non-protective. These data provide some insights on β-glucan epitope(s) mediating antifungal protection and open the way to develop a synthetic oligosaccharide vaccine against fungal diseases.