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Mentions: To explore the combined effect of rPb27 immunization and fluconazole treatment in BALB/c mice, animals immunization and chemotherapy started 30 days after infection. Analysis of organ CFU was done after 40 and 90 days of treatment. A significant reduction of fungi recovered from lung, spleen and liver of animals (CFU) was obtained in mice immunized with rPb27 and treated with fluconazole at the first time point. In the lung of these animals it was determined, 40 days post treatment, a 60% reduction in the CFUs in relation to infected-only group. Besides, in the liver and spleen of these animals there wasn't recovered any fungi colonie at the two time points analyzed. The rPb27 immunization alone failed to reduce fungi recovered from these organs. And the treatment with the antifungal drug alone also failed to reduce the number of CFU in the lung and liver at two time points, and in the spleen after 90 days of treatment despite a reduction after 40 days (Fig. 2 A, B).
Additive Effect of rPb27 Immunization and Chemotherapy in Experimental Paracoccidioidomycosis
Bottom Line: Additionally, in the lungs after 40 days of treatment there was a significant reduction in the fungal load and size of lesions.Moreover, significant levels of anti-rPb27 specific IgG1, IgG2a and IgG2b isotypes were detected in the sera of mice immunized with rPb27 fluconazole treated or not.These results showed an additive protective effect of rPb27 immunization and chemotherapy, suggesting that an rPb27-based vaccine can be used to enhance PCM antifungal treatment.
Affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. firstname.lastname@example.org
Paracoccidioidomycosis, PCM, the major systemic mycosis in Latin America, is caused by the termally dimorphic fungus Paracoccidioides brasiliensis and requires extended periods of chemotherapy with a significant frequency of relapsing disease. The search for new alternatives of treatment is necessary. rPb27 is an antigenic protein from P. brasiliensis that already showed a significant protective activity as a vaccine for PCM in experimental models. The cDNA of rPb27 was subcloned into a pET-DEST 42 plasmid, expressed in E. coli with a his-tag and purified by affinity chromatography. Immunization with this recombinant protein and chemotherapy were used together in an attempt to improve treatment of PCM. For this, BALB/c mice were challenged with pathogenic P. brasiliensis strain and after immunized with rPb27, in the presence of Corynebacterium parvum and Al(OH)(3), some groups were also treated with fluconazole. After 40 days of treatment, the combined drug/rPb27 administration controlled PCM in the liver and spleen, with long lasting protection, and largely preserved tissues structures of these organs. Additionally, in the lungs after 40 days of treatment there was a significant reduction in the fungal load and size of lesions. At the same time, the levels of TNF-α were higher than infected-only mice. Moreover, significant levels of anti-rPb27 specific IgG1, IgG2a and IgG2b isotypes were detected in the sera of mice immunized with rPb27 fluconazole treated or not. These results showed an additive protective effect of rPb27 immunization and chemotherapy, suggesting that an rPb27-based vaccine can be used to enhance PCM antifungal treatment.
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