At present, there are no antifungal vaccines available for the numerous people — in particular, immunocompromised individuals — who are at risk of infection with opportunistic fungal pathogens. However, new hope for the development of an effective vaccine has been provided by data published in The Journal of Experimental Medicine that indicate that immunization with the β-glucan laminarin conjugated to the diphtheria toxoid CRM197 protects mice from infection with Candida albicans and Aspergillus fumigatus.

Fungal infections such as aspergillosis and candidiasis are a serious threat to immunocompromised individuals and have a high mortality rate, even when patients are treated with antifungal drugs, thereby highlighting the pressing need for an effective vaccine. Because β-glucans, a polysaccharide component of fungal cell walls, are essential for fungal viability, they are not expected to mutate readily. So, to develop an immunogen that is likely to induce a β-glucan-specific immune response, Torosantucci et al. linked laminarin, a well-characterized and weakly immunogenic β-glucan from the brown alga Laminaria digitata, to the highly immunogenic diphtheria toxoid CRM197, a protein carrier that is a component of some current human vaccines. Treatment of mice with this conjugate (Lam–CRM) before lethal systemic challenge with C. albicans was protective, in terms of both median survival time and overall mortality. Protection was associated with the presence of β-glucan-specific antibodies, and, when transferred to naive animals, these antibodies markedly reduced the fungal burden in the kidneys of recipients that were subsequently challenged with C. albicans. Similarly, prophylactic treatment of rats with Lam–CRM protected them from disease in a rat model of vaginal candidiasis, and vaginal fluid from immunized rats transferred protection to non-immunized animals in a β-glucan-specific-antibody-dependent manner. Importantly, initial studies also showed that Lam–CRM protects mice against a lethal systemic challenge with another major human fungal pathogen, A. fumigatus.

The β-glucan-specific antibodies were shown to bind the hyphae and germ tubes of C. albicans and the hyphal threads of A. fumigatus and to inhibit fungal growth, providing one potential mechanism by which these antibodies can protect against fungal infection.

These data show that a single carrier-protein-conjugated β-glucan can induce a protective immune response to subsequent challenge with distinct fungal pathogens that cause markedly disparate disease states. Because the authors also showed that a β-glucan-specific monoclonal antibody could reduce fungal burden, they suggest that β-glucan-specific antibodies might also be an effective immunotherapy for patients who are already infected with a fungal pathogen.