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

Abstract

Summary 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.

Decoding Serological Response to Candida Cell Wall Immunome into Novel Diagnostic, Prognostic, and Therapeutic Candidates for Systemic Candidiasis by Proteomic and Bioinformatic Analyses

“…These results are consistent with those of earlier studies in which anti-enolase antibodies were found to be partially protective in experimental SC (88,89) and supports the notion that other protective mechanisms against SC are also implicated (13)(14)(15)90).…”

“…Research efforts currently focus on screening both for Candida cell wall polysaccharides (mannans or ␤-1,3-glucans), extracellular proteins (secreted aspartyl proteinase), cytoplasmic proteins (enolase or heat shock protein 90), metabolites (D-arabinitol), or nucleic acids (DNA or RNA) and for anti-Candida antibodies in body fluids of SC patients (11)(12)(13)(14)(15). The relevance of well defined Candida cell wall proteins or their related antibodies in SC diagnosis, prognosis, and therapy, however, has been barely examined (16 -18).…”

Immune Sensing of Aspergillus fumigatus Proteins, Glycolipids, and Polysaccharides and the Impact on Th Immunity and Vaccination

“…Although the secretion of aspartic proteases has long been recognized as a virulence-associated trait of Candida spp. (38), the vaccinating potential of secreted proteases from Candida (37), and now from Aspergillus, further adds to the biological functions of proteases at the fungus/host interface, as already suggested (39). In this regard, we have recently shown a crucial role for host protease-activated receptors in murine aspergillosis (39).…”

Streptococcus agalactiae GAPDH Is a Virulence-Associated Immunomodulatory Protein

“…Different structural microbial Ags such as LPS or the staphylococcal protein A are known to induce polyclonal B cell activation. In addition, several microbial extracellular proteins including enzymes have also been described as B cell activators (8,13,25,51,52). The ability of microbial constituents to induce polyclonal B cell activation in the infected host constitutes a mechanism of host immune evasion used by pathogens to suppress the specific, potentially protective, immune responses (5,14,21).…”

“…Previous reports showing that immunization against a particular VIP confers protection against the infection caused by the VIP-producing microbe, further indicates the important role of VIP for the success of microbial colonization (11,(22)(23)(24)(25).…”