page 597, Torosantucci and colleagues describe a novel vaccine with the potential to confer protection against multiple fungal pathogens. In mice, the vaccine induced protective immunity against Candida albicans and Aspergillus fumigatus, both common fungal pathogens that prey on immunocompromised individuals.
Effective antifungal therapy can be hampered by drug toxicity and acquired resistance. A therapeutic or prophylactic vaccine might circumvent these problems, but none are commercially available. β-glucan, a polysaccharide component of all pathogenic fungal cell walls, is an attractive antigenic target for vaccine development as it is critical for survival and is not expected to readily mutate in response to immune pressure—a common problem for vaccination against highly mutable proteins such as the HIV envelope protein.
In their study, Torosantucci and colleagues used laminarin, a well-characterized β-glucan from the brown alga Laminaria digita, as a source of immunizing antigen. Laminarin's weak immunogenicity was overcome by hooking it up to the highly immunogenic diptheria toxin, a protein carrier commonly used in human vaccines.
Mice and rats immunized with this vaccine developed anti–β-glucan antibodies and were protected against otherwise lethal challenge with C. albicans and A. fumigatus. Immune serum and a β-glucan specific monoclonal antibody also protected naive mice when transferred intravenously. In vitro, anti–β-glucan antibodies bound preferentially to C. albicans hyphae and inhibited fungal growth in the absence of cells, suggesting that protection was antibody mediated rather than cell mediated. Thus the vaccine might protect individuals with defects in the phagocytic cells that normally attack fungal invaders.
“This is the first time that a single vaccine formulation has been effective against such diverse pathogens as Candida and Aspergillus,” says senior author, Antonio Cassone. The authors now plan to test this vaccine in humans. They also plan to test it against certain bacteria and protozoa known to express glucan or glucan-like molecules.