Immunization with the Candida albicans Membrane Fraction and in Combination with Fluconazole Protects against Systemic Fungal Infections

Abstract

We studied the immunogenicity of a membrane fraction prepared from Candida albicans cells called C. albicans membrane antigen (CMA). The present study revealed that CMA immunization has antifungal activity in mouse models of systemic fungal infection. Immunization of mice by subcutaneous injections of CMA with incomplete Freund adjuvant induced resistance to infections caused not only by C. albicans but also by Aspergillus fumigatus. The level of resistance to candidiasis was as high as that induced by whole-cell immunization. The acquired resistance to candidiasis in the mice immunized with CMA was not diminished by immunosuppressive treatment with cyclophosphamide. The level of resistance to fungal infections was superior to that given by fluconazole (FLC) treatment alone and highly enhanced by the combination with FLC. When CD4؉ cells in CMA-immunized mice were depleted by a monoclonal antibody, the antifungal activity induced by the combination of CMA and FLC was significantly reduced. These results indicate that immunization with CMA is useful for preventing systemic fungal infections and in combination with FLC for increasing resistance after infection.

Protection of Mice from Lethal Endogenous Candida albicans Infection by Immunization with Candida Membrane Antigen

“…Therefore this immunizing procedure can be assumed to be protective for patients facing the risk of systemic candidiasis with endogenous Candida dissemination. This assumption is reasonable because this procedure is highly protective against the intravenous challenge of Candida cells in mice, as reported previously (9,10).…”

“…We speculate that this resistance to Candida infection may include some nonspecific mechanism, which was suggested by a decrease in the number of Candida cells in the kidneys of FA-treated mice (Table 1). This speculation is also supported by the finding that the CMA vaccine induced resistance to Aspergillus infection in mice (9). It is also necessary to analyze what processes of Candida dissemination from the intestinal tract can be prevented by host immunity augmented by CMA immunization.…”

“…The precipitate was washed, suspended in saline, boiled in water for 15 min, and resuspended to form a uniform homogenate with the use of a sonicator (Insonator Model 200 M, Kubota, Tokyo), yielding a purified preparation of CMA. A 2-liter culture containing approximately 2 10 12 cells yielded 1.5 g protein of CMA (9,10). CMA consisted of 60% protein, 8% carbohydrate, and 30% lipid.…”

“…We prepared CMA as previously described (9,10). Briefly, C. albicans TIMM 1768 (1,12,13) was cultured in YPD medium (yeast extract 1%, polypeptone 2%, and glucose 2%) at 35 C overnight with shaking.…”

“…In a preceding paper, Mizutani et al (9,10) reported that a purified cell membrane fraction called Candida membrane antigen (CMA) was a powerful antigen providing protection to mice against experimental candidiasis resulting from the intravenous inoculation of C. albicans.…”