Protection against systemic candidiasis in mice immunized with secreted aspartic proteinase 2.
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.
Laboratório 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
Manuel
M
Vilanova
Luzia
L
Teixeira
Iris
I
Caramalho
Egídio
E
Torrado
Andreia
A
Marques
Pedro
P
Madureira
Adília
A
Ribeiro
Paula
P
Ferreira
Miguel
M
Gama
Jocelyne
J
Demengeot
D000276:Adjuvants, Immunologic; D000818:Animals; D000908:Antibodies, Fungal / Q000032:analysis; D000917:Antibody Formation / Q000276:immunology; D000946:Antigens, Fungal / Q000276:immunology; D016282:Aspartic Acid Endopeptidases / Q000008:administration & dosage / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology*; D005434:Flow Cytometry / Q000379:methods; D005656:Fungal Proteins; D007116:Immunization, Passive / Q000379:methods; D007074:Immunoglobulin G / Q000032:analysis; D007271:Injections, Intradermal; D007668:Kidney / Q000382:microbiology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014611:Vaccination / Q000379:methods*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D000908:Antibodies, Fungal; D000946:Antigens, Fungal; D005656:Fungal Proteins; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; D016282:Aspartic Acid Endopeptidases; C090753:SAP2 protein, Candida