The role of adjuvants in therapeutic protection against paracoccidioidomycosis after immunization with the P10 peptide

Author(s)

Mayorga, Oriana ^[1] ; Munoz, Julian E. ^[1] ; Lincopan, Nilton ^{[1, 2]} ; Teixeira, Aline F. ^[1] ; Ferreira, Luis C. S. ^[1] ; Travassos, Luiz R. ^[3] ; Taborda, Carlos P. ^{[1, 4]}

Affiliation

^[1] Univ Sao Paulo, Dept Microbiol, Biomed Sci Inst, BR-05008900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Pharm, Dept Clin Anal, BR-05008900 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Lab Med Mycol LIM53, IMTSP, BR-05008900 Sao Paulo - Brazil

• Document type: Journal article
• Source: FRONTIERS IN MICROBIOLOGY; v. 3, 2012.
• Web of Science Citations: 16

Abstract

Paracoccidioidomycosis (PCM), a common chronic mycosis in Latin America, is a granulomatous systemic disease caused by the thermo-dimorphic fungus Paracoccidioides brasiliensis. The glycoprotein gp43 is the main antigen target of P brasiliensis and a 15-mer internal peptide (QTLIAIHTLAIRYAN), known as P10, defines a major CD4(+)-specific T cell epitope. Previous results have indicated that, besides having a preventive role in conventional immunizations prior to challenge with the fungus, protective anti-fungal effects can be induced in P brasiliensis-infected mice treated with P10 administered with complete Freund's adjuvant (CFA). The peptide elicits an IFN-gamma-dependent Th1 immune response and is the main candidate for effective immunotherapy of patients with PCM, as an adjunctive approach to conventional chemotherapy. In the present study we tested the therapeutic effects of P10 combined with different adjuvants {[}aluminum hydroxide, CFA, flagellin, and the cationic lipid dioctadecyl-dimethylammonium bromide (DODAB)] in BALB/c mice previously infected with the P brasiliensis Pb18 strain. Significant reductions in the number of colony forming units of the fungus were detected in lungs of mice immunized with P10 associated with the different adjuvants 52 days after infection. Mice treated with DODAB and P10, followed by mice treated with P10 and flagellin, showed the most prominent effects as demonstrated by the lowest numbers of viable yeast cells as well as reductions in granuloma formation and fibrosis. Concomitantly, secretion of IFN-gamma and INF-alpha, in contrast to interleukin (IL)-4 and 11,10, was enhanced in the lungs of mice immunized with P10 in combination with the tested adjuvants, with the best results observed in mice treated with P10 and DODAB. In conclusion, the present results demonstrate that the co-administration of the synthetic P10 peptide with several adjuvants, particularly DODAB, have significant therapeutic effects in experimental PCM. (AU)

• FAPESP's process: 11/17267-4 - Evaluation of a vaccine based on peptide-P10 and the therapeutic effect when administrate in combination with antifungal drugs in the fibrose experimental murine model induzed with Paracoccodioides brasiliensis conidia
• Grantee: Carlos Pelleschi Taborda
• Support Opportunities: Regular Research Grants
• FAPESP's process: 09/15823-7 - Use of dendritic cells from mice and human pulsed with pVAX vector containing insert for the expression of P10 or P10 synthetic peptide derived from the GP 43 of P. brasiliensis, as vaccine strategy against paracoccidioidomycosis
• Grantee: Carlos Pelleschi Taborda
• Support Opportunities: Regular Research Grants