Low virulent strains of Candida albicans: unravelling the antigens for a future vaccine
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Published on: September 16, 2022
Elena Fernández-Arenas1, Gloria Molero, César Nombela
1Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
Abstract:
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.
Insights
A Candida albicans mutant strain, CNC13, demonstrated significant protection against systemic candidiasis in mice. This study identified key immunogenic proteins from CNC13 as potential candidates for a novel fungal vaccine.
Area of Science:
- Mycology
- Immunology
- Vaccine Development
Background:
- Systemic candidiasis remains a significant threat, necessitating effective preventative strategies.
- Attenuated microbial strains are explored as vaccine candidates to elicit protective immunity.
- Understanding the immunogenic components of vaccine strains is crucial for rational vaccine design.
Purpose of the Study:
- To evaluate the efficacy of low-virulent Candida albicans mutant strains as vaccines against systemic candidiasis in a murine model.
- To identify specific immunogenic proteins from a protective vaccine strain using a proteomic approach.
- To define antibody profiles associated with protection induced by the vaccine candidate.
Main Methods:
- Utilized three low-virulent Candida albicans mutant strains (CM1613, CNC13, 92') in a murine model of systemic candidiasis.
- Administered mutant strains as vaccines and subsequently challenged with a lethal dose of wild-type C. albicans.
- Employed a proteomic approach, including 2D gel electrophoresis and mass spectrometry, to identify immunogenic proteins.
- Analyzed antibody responses (isotype IgG2a) in vaccinated and non-vaccinated animals.
Main Results:
- The CNC13 mutant strain induced significant protection, resulting in 60-70% survival in vaccinated mice.
- Proteomic analysis identified 25 immunogenic C. albicans proteins.
- Distinct antibody profiles were observed between surviving (CNC13-vaccinated) and non-vaccinated animals.
- Identified specific antigens, including enolase (Eno1p), pyruvate kinase (Cdc19p), and novel antigens Imh3p and Acs2p, that elicited protective IgG2a antibodies.
Conclusions:
- The CNC13 mutant strain is a promising vaccine candidate for systemic candidiasis, inducing long-lasting protection.
- Proteomic analysis effectively identified key antigens responsible for protective immunity.
- The identified antigenic proteins are strong candidates for the development of a future fungal vaccine.
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