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Published on: November 6, 2020
Protection against systemic candidiasis in mice immunized with secreted aspartic proteinase 2
Manuel Vilanova1, Luzia Teixeira, Iris Caramalho
1Laboratório de Imunologia Mário Arala Chaves, Instituto de Ciências Biomédicas de Abel Salazar, Largo do Prof. Abel Salazar 2, 4099-003 Porto, Portugal. vilanova@icbas.up.pt
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.
Insights
Vaccinating mice with Candida albicans secreted aspartic proteinase 2 (Sap2) significantly reduced kidney colonization in systemic candidiasis. This antibody-mediated protection highlights Sap2 as a promising vaccine target.
Area of Science:
- Mycology
- Immunology
- Vaccinology
Background:
- Secreted aspartic proteinases (Saps) are virulence factors in Candida albicans, contributing to host colonization in candidiasis.
- Systemic candidiasis, induced by intraperitoneal inoculation of C. albicans in mice, leads to rapid kidney colonization.
Purpose of the Study:
- To evaluate the efficacy of vaccination with secreted aspartic proteinase 2 (Sap2) from C. albicans in preventing systemic candidiasis in a mouse model.
Main Methods:
- BALB/c mice were immunized intradermally with purified native Sap2 protein in alum adjuvant.
- Mice were subsequently infected with C. albicans, and kidney colonization was assessed.
- Immune response was evaluated by measuring serum antibodies and through passive transfer of anti-Sap2 IgG.
Main Results:
- Sap2 vaccination with alum adjuvant resulted in a 20-fold decrease in kidney colonization by C. albicans.
- Protection was observed even with a lethal C. albicans inoculum.
- Protection correlated with increased anti-Sap2 serum antibodies, and passive transfer of these antibodies conferred protection, indicating an antibody-mediated mechanism.
Conclusions:
- Secreted aspartic proteinase 2 (Sap2) is a viable vaccination target for preventing systemic candidiasis.
- The protective immunity induced by Sap2 vaccination is mediated by antibodies.
- Sap2 may play an immunomodulatory role in C. albicans infections.
