DNA vaccine encoding peptide P10 against experimental paracoccidioidomycosis induces long-term protection in presence of regulatory T cells

Autor(es)

de Amorim, Juliana ^[1] ; Magalhaes, Adriana ^[1] ; Munoz, Julian Esteban ^[1] ; Rittner, Glauce M. G. ^[1] ; Nosanchuk, Joshua D. ^{[2, 3]} ; Travassos, Luiz R. ^[4] ; Taborda, Carlos P. ^{[1, 5]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Microbiol, Inst Biomed Sci, BR-05508900 Sao Paulo - Brazil

^[2] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 - USA

^[3] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 - USA

^[4] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Lab Med Mycol IMT SP LIM53, BR-05508900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Microbes and Infection; v. 15, n. 3, p. 181-191, MAR 2013.
• Citações Web of Science: 7

Resumo

Paracoccidioidomycosis is a granulomatous systemic mycosis endemic in Brazil and other Latin America countries. A DNA vaccine encoding the inununoprotective peptide 10 (P10) significantly reduced the fungal burden in mice when given prior to or after intratracheal challenge with Paracoccidioides brasiliensis. Presently, the generation/expansion of CD4(+) CD44(hi) memory T cells as well as Foxp3(+) Treg cells in mice immunized with the DNA vaccine (pcDNA3-P10) before and after infection with P. brasiliensis was investigated. Memory CD4(+) CD44(hi) T cells simultaneously with Foxp3(+) Treg cells increased in the spleens and lungs of pcDNA3-P10 immunized mice on day 0, 30, 60 and 120 postinfection. Histopathology of the lung tissue showed minimal inflammation in immunized mice compared with the unimmunized group, suggesting a role for regulatory T cells in controlling the immunopathology. The DNA vaccine shows that the repeated immunization generates memory cells and regulatory T cells that replace the initially protective pro-inflammatory T cells conferring a long term protection while preserving the integrity of the infected tissue. (C) 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved. (AU)

• Processo FAPESP: 11/17267-4 - Avaliação de uma vacina baseada no peptídeo-P10 e seu efeito terapêutico quando administrado em combinação com antifúngicos no modelo da fibrose experimental induzido com conídios de Paracoccidioides Brasiliensis
• Beneficiário: Carlos Pelleschi Taborda
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 09/15823-7 - Utilização de células dendríticas de camundongos e humanas pulsadas com vetor pVAX contendo inserto para expressão de P10 ou peptídeo P10 sintético, derivado da GP 43 de P. brasiliensis, como estratégia vacinal contra a paracoccidioidomicose
• Beneficiário: Carlos Pelleschi Taborda
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/51423-0 - Peptídeos bioativos e peptidases: atividades biológicas e imunobiológicas em doenças infecciosas e no câncer
• Beneficiário: Luiz Rodolpho Raja Gabaglia Travassos
• Modalidade de apoio: Auxílio à Pesquisa - Temático