Immunotherapy against experimental cryptococcosis: a strategy of vaccination with TLR2 agonists as immunostimulating agents

• Grant number: 19/09261-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2019
• End date: June 30, 2020
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Thiago Aparecido da Silva
• Grantee: Júlia Garcia Guimarães
• Host 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 TLR2 agonists as immunostimulant agents within vaccine strategy against C. gattii infection. The cellular activation by TLR2 signaling contributes to the development of a specific immune response against intracellular pathogens, and TLR2 agonists have been used as adjuvants within vaccine protocol for combating bacteria and viruses. The TLR2 agonists have not been evaluated as immunostimulant agent against invasive fungal infections, and we proposed the administration of TLR2 agonists (ArtinM and Pam3CSk4) associated with the inactivated C. gattii yeast as vaccination strategy against experimental cryptococcosis. The vaccination of C57BL/6 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 C57BL/6 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 TLR2 agonist, which can improve the immunotherapy against invasive fungal infections.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MARTINS OLIVEIRA-BRITO, PATRICIA KELLEN; DE CAMPOS, GABRIELA YAMAZAKI; GUIMARAES, JULIA GARCIA; DA COSTA, LETICIA SERAFIM; DE MOURA, EDANIELLE SILVA; LAZO-CHICA, JAVIER EMILIO; ROQUE-BARREIRA, MARIA CRISTINA; DA SILVA, THIAGO APARECIDO. Adjuvant Curdlan Contributes to Immunization against Cryptococcus gattii Infection in a Mouse Strain-Specific Manner. VACCINES, v. 10, n. 4, p. 26-pg., 2022-04-01. (19/13979-1, 19/09261-8, 18/18538-0, 19/09260-1, 18/19949-4, 16/04877-2, 18/21708-5, 19/26074-7)