Protection against systemic candidiasis in mice immunized with secreted aspartic proteinase 2

Abstract

Secreted aspartic proteinases (Sap) have been described as virulence factors implicated in the mechanisms of host colonization by the yeast Candida albicans in different types of candidiasis. Intraperitoneal inoculation of C. albicans into BALB/c mice rapidly leads to systemic candidiasis, with significant colonization of the kidneys measurable in the following week. In this study we assessed the potential of vaccination with C. albicans secreted aspartic proteinase 2 (Sap2) in preventing systemic candidiasis in BALB/c mice. Intradermal injection of highly purified native Sap2 protein incorporated in alum adjuvant provided efficient immune protection, as indicated by a 20-fold decrease in the colonization of kidneys. The protective effect of Sap2 immunization with alum adjuvant was also observed in mice infected with a lethal inoculum of C. albicans. Immunization with the native Sap2 alone, as well as with a denatured recombinant form of the protein, also conferred protection, albeit to a lesser level. In all cases, protection correlated with an increase in serum antibodies to Sap2. Moreover, passive transfer of anti-Sap2 immunoglobulin G (IgG) significantly decreased the yeast burden in kidneys of C. albicans-infected mice. This result shows that immune protection against systemic candidiasis in mice immunized with Sap2 is antibody-mediated. Taken together, these analyses demonstrate that Sap2 can be successfully used as a vaccination target in systemic candidiasis and reveals the potential immunomodulatory role of Sap2 on C. albicans infection.