A novel glyco-conjugate vaccine, composed of a simple β-glucan polysaccharide such as laminarin conjugated with the diphtheria toxoid CRM197, has been shown here to confer protection, when used as preventive vaccine, against both a lethal systemic infection in mice and against a self-healing vaginal C. albicans infection in rats.

Conjugation of laminarin, which by itself is a poor immunogen, with the protein carrier made this polysaccharide immunogenic, as demonstrated by the induction in both rats and mice of anti-β-glucan antibodies, most of which are of the IgG class. No antibodies directed against non–glucan-containing fungal materials, including cell surface mannoproteins, were generated, matching the nonfungal source and purity of both laminarin and carrier protein. High levels of anti-CRM antibodies were induced equally by vaccination with Lam-CRM or with CRM alone, making the use of this latter protein a particularly good control.

Antibody production was essential for anti-Candida protection, as was demonstrated by experiments involving passive transfer of the whole immune serum or its IgG-enriched fraction, which conferred protection to nonimmune animals. Such protection was not conferred by any control serum or when the antibodies present in the Lam-CRM serum were adsorbed on fungal cells or β-glucan particles. Loss of protective capacity on absorption on β-glucan particles and the passive protection conferred by mAb 2G8, an anti-β-glucan mAb, constitute additional although indirect evidence that anti-β-glucan antibodies are largely responsible for the vaccine-induced protection.

Anti-β-glucan antibodies were shown to bind preferentially to the hyphae of C. albicans and to cause inhibition of their growth in vitro in the absence of any host cellular factor. Remarkably, the same vaccine also protected the mice from a lethal infection of A. fumigatus, a fungal organism quite distinct from C. albicans but also expressing β-glucan polysaccharides on its cell wall.

Conclusion 

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