Screening of Paracoccidioides brasiliensis antigens with potential immunotherapeutic application in paracoccidioidomicose

• Grant number: 13/12278-3
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2013
• End date: October 31, 2015
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ademilson Panunto-Castelo
• Grantee: Ademilson Panunto-Castelo
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Paracoccidioidomycosis (PCM) is an infectious disease caused by the dimorphic fungus Paracoccidioides brasiliensis. Among the deep mycoses, PCM is the most prevalent in Latin America and represents a public health problem in Brazil, Argentina, Colombia and Venezuela. Although important advances in immunopathogenesis of PCM have occurred in recent years, small part of that knowledge has been converted into immunotherapy strategies and discoveries of antigen candidates for vaccine and therapeutic targets. Some glycoproteins have received attention as promising candidates, but none of them really proved effective in decreasing the fungal load and lung lesions in experimental PCM. Preliminary results from our group have shown that therapeutic injection of adjuvant modulates immune response to a T helper 1 pattern, which induces protection of mice previously infected with P. brasiliensis. The fact that these adjuvants have been administered in the absence of antigen led us to hypothesize that antigen released during the course of infection could play an important role in the activation of protective host immune response and, consequently, protection. These observations justify the identification of these antigens as molecules that can modulate the immune response and thereby therapeutic targets. The severity of many cases of PCM, absence of an antifungal agent of low toxicity, and also lack of approved vaccines for the treatment of fungal infections of medical importance motivated us to propose the isolation and characterization of antigenic components of P. brasiliensis that can be used to develop a model for immunotherapeutic intervention with induction of specific immunity in chronically infected mice. (AU)

Scientific publications

(5)

(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)

FERNANDES, FABR-CIO FREITAS; DE OLIVEIRA, LEANDRO LICURSI; LANDGRAF, TAISE NATALI; PERON, GABRIELA; COSTA, MARCELO VIEIRA; COELHO-CASTELO, ARLETE A. M.; BONATO, VANIA L. D.; ROQUE-BARREIRA, MARIA-CRISTINA; PANUNTO-CASTELO, ADEMILSON. Detrimental Effect of Fungal 60-kDa Heat Shock Protein on Experimental Paracoccidioides brasiliensis Infection. PLoS One, v. 11, n. 9, SEP 6 2016. (09/03235-3, 13/12278-3, 12/08552-0, 09/14777-1)

G. PERON; F.F. FERNANDES; T.N. LANDGRAF; R. MARTINEZ; A. PANUNTO-CASTELO. Recombinant 60-kDa heat shock protein from Paracoccidioides brasiliensis: is it a good antigen for serological diagnosis of paracoccidioidomycosis?. Brazilian Journal of Medical and Biological Research, v. 50, n. 4, 2017-04-03. (12/08552-0, 13/12278-3, 09/03235-3, 12/07924-0)

LANDGRAF, TAISE NATALI; FERNANDES, FABRICIO FREITAS; PERON, GABRIELA; PANUNTO-CASTELO, ADEMILSON. Therapeutic effect of monophosphoryl lipid A administration on Paracoccidioides brasiliensis-infected mice. Medical Mycology, v. 55, n. 3, p. 344-348, APR 2017. (13/12278-3, 12/08552-0)

COSTA, MARCELO VIEIRA; LANDGRAF, TAISE NATALI; CORREA, PRISCILA C.; LEMOS SOUZA, IGOR EMILIANO; FERNANDES, FABRICIO FREITAS; PANUNTO-CASTELO, ADEMILSON. Quantitation of pulmonary fungal burden in Paracoccidioides brasiliensis-infected mice by real-time PCR. Revista do Instituto de Medicina Tropical de São Paulo, v. 61, 2019. (13/12278-3, 17/01390-8)

LANDGRAF, TAISE N.; COSTA, MARCELO V.; OLIVEIRA, ALINE F.; RIBEIRO, WANDER C.; PANUNTO-CASTELO, ADEMILSON; FERNANDES, FABRICIO F.. Involvement of Dihydrolipoyl Dehydrogenase in the Phagocytosis and Killing of Paracoccidioides brasiliensis by Macrophages. FRONTIERS IN MICROBIOLOGY, v. 8, SEP 20 2017. (16/00629-4, 12/08552-0, 13/12278-3)