The aim of this project is to extend previous clinical and microbiological investigations and, through international collaborations, to understand host-parasite interactions in candidiasis and try to generate novel efficient therapeutic and/or immunological tools. Particularly, we will try to understand the fungal and host components involved in the pathogenesis of mucosal candidiasis and to assess the protective role of recombinant proteins (Sap2 and mannoprotein) as potential candidate vaccines against mucosal candidiasis.
The following specific objectives will be pursued:
- To assess the protective role of recombinant proteins (Sap2 and mannoproteins) as potential candidate vaccine against mucosal candidiasis
- Evaluation of protective role of vaginal dendritic cells in mucosal candidiasis .
- Isolation and identification of Candida spp. from vaginal fluids taken from women with recurrent vaginitis and carriers.
- Detection of cytokine expression in women with recurrent vaginitis and carriers.
- Expression of C. albicans proteinase genes in the oral and vaginal fluids by RT-PCR and Real time PCR.
Evaluation of pathogenicity of Candida isolates in animal models .
The aim of our work is to characterize, in an animal model of vaginal candidiasis, the proper targets for new strategies for vaccination or immunotherapy of vaginal candidiasis. Overall, our data provide a clear evidence that is possible to prevent C. albicans vaginal infection by active intravaginal immunization with aspartyl proteinase (Sap2). The recombinant protein Sap2 was assembled with virosomes and a vaccine PEV 7 was obtained. The results provided evidence that the vaccine constituted by virosomal and Sap2 (PEV7) has an encouraging therapeutic potential for the treatment of recurrent vulvovaginal candidiasis.
The transition of C. albicans from commensal to invasive pathogen is primarily the consequence of a defective host cellular immune response, but of some relevance can be also the virulence of C. albicans strains. Enzyme secretion in particular aspartic proteinase (Sap), plays a role in vaginal candidiasis. We investigate C.albicans OPI1genes that regulate the transcription of Sap2 in C. albicans. The mutant with OPI1 genes deleted affect virulence in a rat model of vaginitis. This becouse OPI1 gene regulates expression of the SAP2 protease, which is required for rat vaginal infections.
YL Chen, F De Bernardis, SJ Yu, S Sandini, S Kauffman, R Tams, E Bethea, TB Reynolds. Candida albicans OPI1 regulates filamentous growth and virulence in vaginal infections, but not inositol biosynthesis. Plos One (2015) 10,e0116974 (Link here to the article)
F De Bernardis, S Arancia, S Sandini, S Graziani, S Norelli. Studies of Immune Responses in Candida vaginitis. Pathogens 2015, 4, 697-707. (Link here to the article)