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Dectin-1 ligands as immunostimulant agents in a vaccination strategy against experimental cryptococcosis

Grant number: 19/09260-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2019
Effective date (End): June 30, 2020
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Principal researcher:Thiago Aparecido da Silva
Grantee:Letícia Serafim da Costa
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The main genus or species of fungi with impact in the global public health related to the last years are: Aspergillus, Candida, Cryptococcus, Pneumocystis jirovecii, and Histoplasma capsulatum. In the case of Cryptococcus gattii, which has relevance due the impact under immunocomprised and immunocompetent individuals. Thus, C. gattii has some mechanisms to subvert the innate and adaptive immune systems, as described for blocking of CD4+ T helper (Th) 1 and Th17 cells. The various PAMPs on the C. gattii surface are associated with the subversion of the host immune response. Some studies are interesting to avoid this situation by vaccination against cryptococcosis, however, different immunization protocols are necessary to eliminate the C. gattii infection. Then, the current proposal aims to evaluate the effect of Dectin-1 agonists as immunostimulant agents within vaccine strategy against C. gattii infection. The cellular activation by Dectin-1 signaling contributes to the development of a specific immune response against intracellular pathogens, and Dectin-1 agonists have been used as adjuvants within vaccine protocol for combating bacteria and viruses. We proposed the administration of Dectin-1 agonists (²-glucan peptide and ²-glucan particle) associated with the inactivated C. gattii yeast as vaccination strategy against experimental cryptococcosis. The vaccination of BALB/c mice using intranasal administration will occur for three periods with interval of 7 days. After 7, 14 and 21 days of last vaccination, blood, lung, brain and/or spleen will be collected to analyze the host immune response profile generated by vaccine strategy. Once this immunotherapy strategy is evaluated, the immunization protocol will be applied in BALB/c mice to challenge with C. gattii yeast, and after 21 days of infection the fungal burden and host immune response will be evaluated, and also other factors. Our results can open perspectives to create different immunization protocols against C. gattii infection, as the expression of C. gattii antigens linked to Dectin-1 agonist, which can improve the immunotherapy against invasive fungal infections.

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