Low virulent strains of Candida albicans: unravelling the antigens for a future vaccine.
Several low virulent Candida albicans mutant strains: CM1613 (deleted in the Mitogen Activated Protein (MAP) Kinase MKC1), CNC13 (deleted in the MAP-kinase HOG1) and the morphological mutant 92' were used as vaccines employing a murine model of systemic candidiasis. In this vaccination trial, only the CNC13 strain was able to induce protection against a subsequent infection with a lethal dose of the wild-type strain. The protection induced by CNC13 vaccinated animals resulted in 60-70% percent of survival. These results demonstrate that collaboration between cellular and humoral responses, induced by the CNC13 mutant, elicited a long lasting and effective protection. Using a proteomic approach (two-dimensional gel electrophoresis followed by Western blotting), twenty-five C. albicans immunogenic proteins were detected and identified by matrix-assisted laser desorption/ionization and/or tandem mass spectrometry. We were able to define an antibody pattern in the sera from the nonvaccinating strains (92' and CM1613), which was different from the profile detected in the sera from surviving animals (vaccinated with the CNC13 mutant). The utility of this proteomic approach has allowed us to identify antigens that induce protective IgG2a antibody isotype in the sera from vaccinated animals: enolase (Eno1p), pyruvate kinase (Cdc19p), pyruvate decarboxylase (Pdc11p), a component from the 40S ribosomal subunit (Bel1p), triosephosphate isomerase (Tpi1p), DL-glycerol phosphatase (Rhr2p), fructose-bisphosphate aldolase (Fba1p) and two new protective antigens: IMP dehydrogenase (Imh3p), and acetyl-CoA synthetase (Acs2p). The antigenic proteins that promote protective antibodies described in this work are excellent candidates for a future fungal vaccine; their heterologous expression and vaccine design is currently underway.
Fernández-Arenas
Elena
E
Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
Molero
Gloria
G
Nombela
César
C
Diez-Orejas
Rosalía
R
Gil
Concha
C
D000818:Animals; D000946:Antigens, Fungal / Q000737:chemistry*; D015153:Blotting, Western; D002176:Candida albicans / Q000235:genetics* / Q000472:pathogenicity*; D003593:Cytoplasm / Q000378:metabolism; D019992:Databases as Topic; D015180:Electrophoresis, Gel, Two-Dimensional; D005657:Fungal Vaccines / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D015151:Immunoblotting; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009154:Mutation; D020543:Proteome; D040901:Proteomics; D011523:Protoplasts / Q000378:metabolism; D016622:Silver Staining; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013601:T-Lymphocytes / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D014774:Virulence
D000946:Antigens, Fungal; D005657:Fungal Vaccines; D020543:Proteome