Identification of antigens from Paracoccidioides brasiliensis with immunotherapeutic potential for the treatment of paracoccidioidomycosis.

• Grant number: 12/08552-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2012
• End date: May 31, 2016
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Ademilson Panunto-Castelo
• Grantee: Taise Natali Landgraf
• 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, the PCM is the most prevalent in Latin American and represents an important public health problem in countries where there is a high incidence of the disease - Brazil, Argentina, Colombia and Venezuela. Although important advances in the immunopathogenesis of PCM occurred in recent years, small portion of this knowledge have been converted into immunotherapy strategies and discoveries of antigens candidates for vaccine and therapeutic targets. Some glycoproteins have received attention as promising candidates, but none of them actually proved effective in reducing fungal burden and lung lesions in experimental PCM. Preliminary results from our group have shown that injection of adjuvant therapy that predisposes the immune response of T helper 1 pattern, protective in PCM, induces protection of mice previously infected with P. brasiliensis. The fact that these adjuvants have been administered in the absence of antigens gave rise to the hypothesis that antigens liberated during the course of infection could play an important role in protection observed and consequently, the activation of the host immune system. These observations justify the identification of these antigens such as molecules that can modulate the immune response and so that therapeutic targets. The severity of the clinical presentation of PCM plus the absence of an antifungal agent of low toxicity, and also the lack of approved vaccines for the treatment of fungal infections of medical importance motive us to propose the isolation and characterization of antigenic components of P. brasiliensis which can be used to develop a model for immunotherapeutic intervention, whose induction of specific immunity occur in mice infected chronically.

Scientific publications

(4)

(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)

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)

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)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

LANDGRAF, Taise Natali. Monophosphoryl lipid A and diidrolipoil dehydrogenase from Paracoccidioides brasiliensis have therapeutic effect on experimental paracoccidioidomycosis. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.