Presentation by human dendritic cells of peptides with vaccine capacity and prospection of pan-fungal antigens in paracoccidioidomycosis

• Grant number: 17/25780-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2018
• End date: November 30, 2022
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Carlos Pelleschi Taborda
• Grantee: Suélen Andreia Rossi
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 16/08730-6 - Fungal pathogenicity: environmental effects, immune response and vaccine modulation in the Brazilian endemic mycoses paracoccidioidomycosis and histoplasmosis, AP.TEM
• Associated scholarship(s): 20/09919-0 - Production and evaluation of the use of 2D and 3D lung organoid in host pathogen interaction and analysis of the effect of chitosan nanoparticles, BE.EP.PD

Abstract

The Paracoccidioidomycosis (PCM) is a systemic Mycosis endemic in Latin America caused by thermo-dimorphic fungus of the Paracoccidioides genus and is mainly associated to agricultural activities and rural environments. Brazil is the country with more than 80% of all cases of PCM reported, and even with several therapeutic options available for treatment, PCM regimens require prolonged administration, increasing the costs and toxicity of therapy. The gp43 is a glycoprotein of 416 amino acids with important immunoprotective function already proved. A specific fragment of this antigen, which has 15 amino acids, called P10, has already shown solid results in experimental models, and its protective effect against P. brasiliensis has been proven. Recently, in another study developed by our group, it was possible to identify a peptide of 14 alanine residues from P. lutzii isolates. This peptide is between amino acids 72 and 85 of a hypothetical protein of Pb18 (P. brasiliensis) and Pb01 (P. lutzii), covering 7% of the sequence. The main objective of this project is to study the interaction with human dendritic cells and the immune response generated against the fungus after stimulus with the peptide P10 and the peptide composed of 14 alanines, designated as P14A. The possible activation of human dendritic cells against these peptides is a promising step in the development of a vaccine against PCM. Regarding P. lutzii, the glycoprotein gp43, orthologous in this species, is known to be less expressed and has few epitopes in common with the gp43 of the P. brasiliensis. Therefore, new strategies in the search for a safe and effective vaccine against PCM should be explored. In parallel, in vitro and in vivo experiments will be carried out using two types of conjugated polysaccharides, inulin and chitosan, with the general aim of verifying the immunomodulatory effects of the fusion of these polysaccharides against infections by both Paracoccidioides species. (AU)

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)

KISCHKEL, BRENDA; BONICHE-ALFARO, CAMILA; MENEZES, ISABELA DE GODOY; ROSSI, SUELEN ANDREIA; ANGELI, CLAUDIA BLANES; DE ALMEIDA, SANDRO ROGERIO; PALMISANO, GIUSEPPE; LOPES-BEZERRA, LEILA; NOSANCHUK, JOSHUA D.; TABORDA, CARLOS PELLESCHI. Immunoproteomic and Immunopeptidomic Analyses of Histoplasma capsulatum Reveal Promiscuous and Conserved Epitopes Among Fungi With Vaccine Potential. FRONTIERS IN IMMUNOLOGY, v. 12, NOV 22 2021. (18/18257-1, 16/08730-6, 14/06863-3, 17/25780-0, 18/26402-1, 18/15549-1)

BONICHE, CAMILA; ROSSI, SUELEN ANDREIA; KISCHKEL, BRENDA; BARBALHO, FILIPE VIEIRA; D'AUREA MOURA, AGATA NOGUEIRA; NOSANCHUK, JOSHUA D.; TRAVASSOS, LUIZ R.; TABORDA, CARLOS PELLESCHI. Immunotherapy against Systemic Fungal Infections Based on Monoclonal Antibodies. JOURNAL OF FUNGI, v. 6, n. 1, MAR 2020. (18/26402-1, 16/08730-6, 17/25780-0)