Immunisation with the glycolytic enzyme enolase confers effective protection against Candida albicans infection in mice

Candida albicans is an opportunistic human fungal pathogen that continues to be a leading cause of candidal infections in immunocompromised hosts. Enolase, an important glycolytic enzyme located on the cell wall of C. albicans, was cloned, purified, and characterized by molecular cloning, affinity chromatography and Western blotting. C57BL/6J mice were immunized with recombinant enolase subcutaneously every two weeks, and the protective effect against systemic challenge evaluated by fungal burdens in target organs, titres of specific antibodies to enolase, and by levels of Th1/2 cytokines in serum. After challenge with C. albicans strains SC5314 and 3630, fungal burdens in the liver, kidney, brain, spleen and lung were significantly decreased in immunized mice. Histopathological assessment demonstrated that enolase protected the tissue structure, and decreased the infiltration of inflammatory cells. The titres of enolase-specific IgG1 and IgG2a in the immune serum reached up to 1:51200. Furthermore, opsonization with immune serum resulted in enhanced killing of both 3630 and SC5314 by murine neutrophils. Levels of IL-12 and IL-8 in the immune serum increased, whereas the concentration of the Th2 cytokine, IL-10, was significantly higher in immunized mice compared to the control group. It was concluded that recombinant enolase effectively protected mice against disseminated candidiasis, and may be a promising target for vaccination against different strains of C. albicans.

Highlights: ► Mice were immunized with recombinant enolase. ► High levels of IgG1 and IgG2a were induced in immune serum. Killing capacity of neutrophils enhanced after yeasts were opsonized with anti-serum. Fungal burdens reduced after antibody were passive transferred. ► Both Th1 cytokine IL-12 and Th2 cytokine IL-10 increased in immune serum. ► Enolase can effectively protect against systemic infection caused by two strains of Candida albicans differing in virulence in mice.