Combined p10 immunization and chemotherapy in mice challenged intratracheally with Paracoccidioides brasiliensis (2006)
- Autor:
- Autor USP: TABORDA, CARLOS PELLESCHI - ICB
- Unidade: ICB
- Assunto: MICROBIOLOGIA
- Language: Inglês
- Abstract: Previous work has shown that the major diagnostic antigen of P. brasiliensis, the gp43, elicits a vigorous IFN-gamma-mediated TCD4+ response that is protective against the intratracheal challenge by virulent yeasts of this fungus. The epitope has been mapped to a 15-aa peptide (P10) that is presented by 3 MHC class II molecules from different mouse haplotypes. The promiscuous nature of P10 was extended to human HLA-DR molecules, as it was shown that this peptide and the analogous gp43 (180-194) without C-terminal asparine (glycosylation site in the original gp43) and with N-terminal lysine, bound to 9 most prevalent HLA-DR molecules. Furthermore, 4 additional peptides from gp43 were also promiscuous with respect to HLA-DR binding. The gp43 (180- 194) was recognized by 53% of patients with treated PCM and the other promiscuous peptides were recognized by 32% to 47% of patients; 74% of patients recognized the combination of 5 promiscuous gp43 peptides. These results are the basis for devising a peptide vaccine against PCM that could be used as an adjuvant to chemotherapy. The demonstration that peptide immunization and chemotherapy combined confer increased protection in experimental PCM is a necessary step in this study. Presently, we used P10 immunization along with amphotericin B, ketoconazole, fluconazole, itraconazole, sulphamethoxazole and sulphamethoxazole-trimethoprim treatment to evaluate the protection against P. brasiliensis infection. Methods: Twodifferent protocols were used. After intratracheal infection of male Balb/c mice with 3 x10 5 yeast cells, drug treatment (for 30 days every 24 h) was started after 48h or after 30 days of i.t. infection. One group of animals was infected and treated with drugs and another was, in addition, also weekly immunized with 20 ug P10. Mice were sacrificed 30 and 90 days or 60 and 120 days after i.t. infection, and the fungal burden measured as lung, liver and spleen CFUs. Organ homogenates were also assayed for cytokines using ELISA kits. Results: Using protocol 1, both treatments with drugs and P10 significantly reduced lung CFUs and showed a synergistical effect after 90 days preventing dissemination to liver and spleen. The only relapse obtained with sulphamethoxazole after 90 days was controled by P10 immunization. Using protocol 2 basically the same results were obtained. Using protocol 1 after 90 days there was a tendency to decreased IL-4 and IL-10 and increased IFNgamma levels in animals immunized with P10. Using protocol 2 the untreated animal group showed higher levels of IL-4 and IL-10 whereas P10 immunization led higher IL-12 and IFN-gamma levels alone or combined with chemotherapy. Conclusion: Synergistical protection using chemotherapy and P10 immunization supports the adjuvant vaccination of patients with promiscuous peptides to reduce the time of treatment and eventually control anergic cases of paracoccidioidomycosis.
- Imprenta:
- Publisher: American Society for Microbiology
- Publisher place: Denver
- Date published: 2006
- Source:
- Título: Abstracts
- Conference titles: ASM Conference on Dimorphic Fungal Pathogens
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ABNT
TABORDA, Carlos Pelleschi. Combined p10 immunization and chemotherapy in mice challenged intratracheally with Paracoccidioides brasiliensis. 2006, Anais.. Denver: American Society for Microbiology, 2006. . Acesso em: 16 fev. 2026. -
APA
Taborda, C. P. (2006). Combined p10 immunization and chemotherapy in mice challenged intratracheally with Paracoccidioides brasiliensis. In Abstracts. Denver: American Society for Microbiology. -
NLM
Taborda CP. Combined p10 immunization and chemotherapy in mice challenged intratracheally with Paracoccidioides brasiliensis. Abstracts. 2006 ;[citado 2026 fev. 16 ] -
Vancouver
Taborda CP. Combined p10 immunization and chemotherapy in mice challenged intratracheally with Paracoccidioides brasiliensis. Abstracts. 2006 ;[citado 2026 fev. 16 ] - Saps1-3 antigens in Candida albicans: differential modulation following exposure to soluble proteins, mammalian cells, and infection in mice
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