Prophylactic and Therapeutic Vaccination Using Dendritic Cells Primed with Peptide 10 Derived from the 43-Kilodalton Glycoprotein of Paracoccidioides brasiliensis

Autor(es)

Magalhaes, A. ^[1] ; Ferreira, K. S. ^[2] ; Almeida, S. R. ^[3] ; Nosanchuk, J. D. ^{[4, 5]} ; Travassos, L. R. ^[6] ; Taborda, C. P. ^{[1, 7]}

Afiliação do(s) autor(es)

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

^[2] Univ Fed Sao Paulo, Dept Biol Sci, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Dept Clin & Toxicol Anal, Fac Pharmaceut Sci, Sao Paulo - Brazil

^[4] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 - USA

^[5] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 - USA

^[6] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Sao Paulo - Brazil

^[7] Univ Sao Paulo, Lab Med Mycol IMT SP LIM53, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Clinical and Vaccine Immunology; v. 19, n. 1, p. 23-29, JAN 2012.
• Citações Web of Science: 25

Resumo

Vaccination with peptide 10 (P10), derived from the Paracoccidioides brasiliensis glycoprotein 43 (gp43), induces a Th1 response that protects mice in an intratracheal P. brasiliensis infection model. Combining P10 with complete Freund's adjuvant (CFA) or other adjuvants further increases the peptide's antifungal effect. Since dendritic cells (DCs) are up to 1,000-fold more efficient at activating T cells than CFA, we examined the impact of P10-primed bone-marrow-derived DC vaccination in mice. Splenocytes from mice immunized with P10 were stimulated in vitro with P10 or P10-primed DCs. T cell proliferation was significantly increased in the presence of P10-primed DCs compared to the peptide. The protective efficacy of P10-primed DCs was studied in an intratracheal P. brasiliensis model in BALB/c mice. Administration of P10-primed DCs prior to (via subcutaneous vaccination) or weeks after (via either subcutaneous or intravenous injection) P. brasiliensis infection decreased pulmonary damage and significantly reduced fungal burdens. The protective response mediated by the injection of primed DCs was characterized mainly by an increased production of gamma interferon (IFN-gamma) and interleukin 12 (IL-12) and a reduction in IL-10 and IL-4 compared to those of infected mice that received saline or unprimed DCs. Hence, our data demonstrate the potential of P10-primed DCs as a vaccine capable of both the rapid protection against the development of serious paracoccidioidomycosis or the treatment of established P. brasiliensis disease. (AU)

• 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