XI International Meeting on Paracoccidioidomycosis

XI International Meeting on Paracoccidioidomycosis

Resume:148-1

Poster (Painel)

148-1

Selection of adjuvants for P10 immunization in the treatment of ਀攀砀瀀攀爀椀洀攀渀琀愀氀瀀愀爀愀挀漀挀挀椀搀椀漀椀搀漀洀礀挀漀猀椀猀

Authors:

Oriana Mayorga Nader (ICB II - USP - Instituto de Ciencias Biomedicas, Dep. de Microbiologia) ; Julian Esteban Muñoz (ICB II - USP - Instituto de Ciencias Biomedicas, Dep. de Microbiologia) ; Nilton Erbet Lincopan Huenuman (ICB II - USP - Instituto de Ciencias Biomedicas, Dep. de Microbiologia) ; Luis Carlos de Souza Ferreira (ICB II - USP - Instituto de Ciencias Biomedicas, Dep. de Microbiologia) ; Luiz Rodolpho Raja Gabaglia Travassos (UNIFESP - Universidade Federal de São Paulo) ; Carlos Pelleschi Taborda (ICB II - USP - Instituto de Ciencias Biomedicas, Dep. de MicrobiologiaIMT/SP-USP - Instituto de Medicina Tropical, Lab. de Micologia Médica)

Abstract

Paracoccidioidomycosis (PCM), the prevailing chronic mycosis in Latin America, is a granulomatous systemic disease caused by the thermo-dimorphic fungus Paracoccidioides brasiliensis. Conidia are formed in saprophytic mycelia and may start a lung infection. Historically, protection against paracoccidioidomycosis has been attributed to a vigorous cellular immune response whereas high levels of specific antibodies have been associated with disease severity. The gp43 is the main diagnostic antigen which contains the 15-mer peptide (QTLIAIHTLAIRYAN), knows as P10, that elicits an IFN-gamma dependent Th1 immune response and is the main candidate for effective immunotherapy of patients with PCM, adjuvant to conventional chemotherapy. Previous results showed the protective effect of P10 immunized with Complete Freund Adjuvant in susceptible mice. Presently, we compared the effectiveness of different adjuvants in BALB/c mice intratracheally infected with 3x105 yeast cells of Pb18. The activities of Aluminum hydroxide, Complete Freund Adjuvant, Salmonella enterica fliC flagellin and the cationic lipid, dioctadecyl-dimethylammonium bromide, associated or not with P10, were tested. A significant reduction in the number of colony forming units (CFUs) from lungs of mice immunized with P10 associated with the different adjuvants was observed after 70 days of infection. The cationic lipid and P10 achieved the best results, with fewer CFUs, reduced fibrosis as determined by staining with Masson’s trichrome and fewer yeast cells in the lung tissue determined by staining with hematoxylin-eosin with a significant increase of IFN-gamma and TNF-alpha and reduced synthesis of IL-4 and IL-10. The results suggest that the association of P10 and the cationic lipid may effectively treat experimental paracoccidiodomycosis.

Keyword: Adjuvant, P10, Cationic Lipid, Immune response, Paracoccidioides brasiliensis

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